CN109715059A - For a group method and system for characterization - Google Patents

For a group method and system for characterization Download PDF

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Publication number
CN109715059A
CN109715059A CN201780057144.2A CN201780057144A CN109715059A CN 109715059 A CN109715059 A CN 109715059A CN 201780057144 A CN201780057144 A CN 201780057144A CN 109715059 A CN109715059 A CN 109715059A
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group
category
user
lactobacillus
microorganism
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丹尼尔·阿尔莫纳西德
劳伦斯·克拉尔
弗朗西斯科·奥桑顿
胡安·巴勃罗·卡德纳斯
杰西卡·里奇曼
扎迦利·阿普特
伊丽莎白·比克
奥德丽·戈达德
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Prosomegen
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Youbi Omux Co
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Abstract

The embodiment of system and method for characterizing illness group can include taxonomy database, wherein the illness group is related to there is the related taxonomical unit set of microorganism, and the taxonomy database includes the reference microorganism feature for taxonomical unit set relevant to the illness group；Processing can be operated to collect the container for including biomaterial from user, and processing system includes the sequenator system that can be operated to determine microorganism sequence data set；With a group characterization system, its can operate with: user's microbial population feature for taxonomical unit set described in user is determined based on the microorganism sequence data set, generate user's microbial population feature with it is described with reference between microbial population feature compared with, and based on the comparison determine user's illness group group characterization；And treatment system, the treatment to promote the illness for the illness group based on described group of characterization can be operated.

Description

For a group method and system for characterization
Cross reference to related applications
The application is that (it is in October, 2015 for the Application U.S. Serial No 15/606,743 submitted on May 26th, 2017 The connecting of the U. S. application for the Serial No. 14/919,614 submitted for 21st) continuation in part application, it is required that in 2014 10 The moon submit within 21st Serial No. 62/066,369 U.S. Provisional Application, in the Serial No. submitted on December 04th, 2014 The interim Shen in the U.S. of 62/087,551 U.S. Provisional Application, the Serial No. 62/092,999 submitted on December 17th, 2014 Please, the U.S. Provisional Application for the sequence number 62/147,376 submitted on April 14th, 2015, submit on April 14th, 2015 The beauty of the U.S. Provisional Application of Serial No. 62/147,212, the Serial No. 62/147,362 submitted on April 14th, 2015 State's provisional application, the U.S. Provisional Application for the Serial No. 62/146,855 submitted on April 13rd, 2015 and in 2015 8 The equity of the U.S. Provisional Application for the Serial No. 62/206,654 that the moon is submitted on the 18th, these applications are whole simultaneously each by reference Enter herein.The application also requires U.S.Provisional Serial 62/395,939,2017 years 6 submitted within 16th in September in 2017 The U.S. Provisional Application sequence that the U.S.Provisional Serial that the moon is submitted on the 15th is submitted on June 27th, 62/520,058 and 2017 The equity of row number 62/525,379, these applications are integrally incorporated herein each by reference.
Technical field
Present invention relates in general to microbiological arts, and relate more specifically in microbiological art for characterizing illness The new and useful method and system of group.
Detailed description of the invention
Figure 1A -1B is the flow chart expression for the modification for the embodiment for characterizing the method for illness group；
Fig. 2 is the flow chart expression for the modification for the embodiment for characterizing the method for illness group；
Fig. 3 is that the schematic diagram of the embodiment of system indicates；
Fig. 4 is that the schematic diagram of the modification of the embodiment of method indicates；
Fig. 5 is that the schematic diagram of the process in the modification for characterizing the method for illness group indicates；
Fig. 6 is the graph representation for the example for determining the Optimal Parameters of target classification unit；
Fig. 7 is the graphical representation of the example of the verifying of characterization process；
Fig. 8 is graph representation of the health with reference to the example of relative abundance range；
Fig. 9 A-9B is the example of target classification unit；
Figure 10 is example of the selection for the probiotics of characterization；
Figure 11-12 is the example of probiotics and associated taxon group；
Figure 13 A-13B is the example of the associated relative abundance of grouping sheet hyte related with probiotics；With
Figure 14-15 is the example at interface.
Specific embodiment
The description of embodiment of the present invention is had no intention below to limit the invention to these embodiments, and is intended to make this Field technical staff is able to carry out and uses the present invention.
1, it summarizes
As shown in figure 3, for characterizing the relevant illness of related to microorganism taxonomical unit set (for example, and alimentary canal (gut) associated disease) embodiment of system 200 of group (for example, multiple) can include taxonomy database 205 comprising with disease The reference microbial population feature of the relevant taxonomical unit set of disease group is (for example, microbial population Diversity Characteristics；Micro- life Object group is functional diversity feature；Microbial population pharmacogenomics feature；Deng)；Processing system 210 is (for example, sample treatment System etc.), can operate with from user (for example, human experimenter, patient, animal subjects, Environment-Ecosystem, nursing Supplier etc.) collect include biomaterial (for example, nucleic acid material etc.) container, processing system 210 include can operate with from Biomaterial determines the sequenator system of the microorganism sequence data set of user；Group characterization system 220, can operate with base Determine user's microbial population feature of the taxonomical unit set of user (for example, relative abundance model in microorganism sequence data set Enclose), generate user's microbial population feature and with reference between microbial population feature (for example, with reference to relative abundance range etc.) Compare, and based on the group characterization for relatively determining user's illness group；With treatment system 230 can operate with based on described group of characterization come Promote the treatment for the illness of the illness group (for example, the treatment can be operated to adjust user's microbial population and form To improve the state etc. of the illness).
Method 100 and/or system 200 can be used for the biological sample based on user, characterize for user across multiple taxonomical units (for example, across multiple kinds and belong to microorganism) microbial population composition and/or microbial population functional diversity, with characterization with The relevant multiple illnesss of multiple taxonomical units.In modification, method 100 and/or system 200 can be used for based on from multiple users Multiple biological samples, be generated at substantially the same time the characterization to multiple users in a multiplexed manner.However, method 100 and/ Or system 200 can with each by reference be integrally incorporated the U. S. application No.14/593 submitted the 9 days January in 2015 of this paper, The 424 any modes similar with mode described in the U. S. application No.14/919,614 that on October 21st, 2015 submits act as With, and/or can work in any suitable manner.Method 100 and/or system 200 can additionally or alternatively be used to promote (example Such as, provide) (therapies) (for example, treatment (treatments) etc.) is treated (such as treating pair of the illness of illness group The remedy measures (for example, based on group characterization) of user) and/or any suitable function of execution.System 200 and/or method 100 Modification can further promote to monitor and/or adjust the such therapy for being supplied to subject, for example, by during the entire course for the treatment of Receive, other samples (for example, for assessing and/or improving multiple illnesss from group) of processing and analysis from subject.
In instances, method 100 and/or system 200 can generate and/or promote the characterization and/or treatment to illness group, Including one or more in following item: symptom, the cause of disease, disease, imbalance, microbial population pharmacogenomics spectrum (for example, Resistance and/or sensibility to antibiotic is described) and/or any other suitable aspect relevant to this group of illness.The illness Group preferably includes any one of alimentary canal associated disease group, including following item or more: ventosity, abdominal distension, diarrhea, Gastroenteritis, indigestion, abdominal pain, abdominal tenderness, constipation, infection, cancer, ecological disturbance, irritable bowel syndrome (IBS), inflammation Property enteropathy (IBD), ulcerative colitis, Crohn disease, celiaca, enteron aisle control problem (such as incontinence of faces), lactose intolerance Disease, diverticulosis, diverticulitis, regurgitation of gastric juice (such as GER, GERD), congenital megacolon, peritoneal adhesion, ecphyaditis, colon breath Meat, food origin disease, gall stone, gastritis, gastroparesis, hemorrhage of gastrointestinal tract, hemorrhoid, pancreatitis, ulcer, Whipple disease, Zuo Linge- Ai Lisen syndrome, associated disease and/or any other suitable alimentary canal associated disease.Additionally or alternatively, the illness Group may include one of following item or more: probiotics is in relation to illness (for example, with the grouping sheet hyte that includes in probiotics Correlation is being affected by it and/or other related with grouping sheet hyte that is including in probiotics；It can be prebiotic with one or more Bacterium treatment；Deng)；Vagina is in relation to illness (such as human papilloma virus infection, syphilis, cervical carcinoma, high-level and low level squama Lesion, Sex transmitted pathogen, cervicitis, pelvic inflammatory disease, bacterial vaginosis BV, aerobic vaginitis, congenital infertility in columnar epithelium Deng)；Spiritual and behavior illness (such as mental handicape；Depression；Amentia；Anxiety disorder etc.)；Illness (example related with communication Such as, expressive language disorder；Stutter；Voice disorder；Self-closing disease；Sound illness；Hearing illness；Ocular disorder etc.；)；With sleep Related illness (such as insomnia, sleep apnea etc.)；The related illness of angiocarpy (such as coronary artery disease；Hypertension etc.)； It is metabolized related illness (such as diabetes etc.), the related illness of rheumatoid disease (such as arthritis etc.)；The related illness of weight is (such as obesity Deng)；The related illness of pain；The related illness of endocrine；The related illness of heredity；Chronic disease；And/or the disease of any other suitable type Disease.However, method 100 and/or system 200 can configure in any suitable manner.
2, benefit
Microbial population analysis is able to achieve to being caused by microorganism and/or otherwise illness group relevant to microorganism Accurate and Efficient Characterization and/or treatment supply.The technology can overcome conventional method in the characterization to illness and/or promote treatment Several challenges faced.Firstly, conventional method, which needs patient to access one or more caregivers, is directed to illness to receive Characterization and/or treatment recommendations, this is equivalent to and diagnoses/or treatment before the time quantum passed is relevant inefficient and health wind Danger.Secondly, conventional method needs to be implemented many different diagnostic tests to characterize illness group, this can also lead to inefficiency and be good for Health risk.Again, the conventional gene sequencing for human genome sequencing and the analytical technology (example when being applied to microbial population Such as, wherein human microbial group system can include microbial cell more than human cell more than 10 times；Wherein optimize sample treatment Technology can be different；The scaling sample treatment program for wherein characterizing illness group can be different；Wherein implant treatment may be different；Wherein sequence Column reference database can be different；Wherein microbial population can change etc. between the different body regions of user) it may be not phase It is holding and/or inefficient.4th, sequencing technologies (for example, next-generation sequencing) if not appearance caused and inhereditary material is sequenced The unprecedented development that relevant speed and data generate will not (for example, data processing problem, with The problem of multiplex mode processing, information display problem, microbial population problem analysis, treatment forecasting problem, treatment supply Problem etc.).The example of system 200 and method 100 can provide the solution of technology origin at least the above challenge.
First, which can be assigned by promoting the computer performance of previously not executable function to computer correlation Technology is (for example, characterization and/or the treatment-related modeling of promotion with illness group；Improve storage, retrieval and/or processing for disease The computational efficiency of the microorganism related data of disease group；Calculation processing relevant to biological sample processing etc.) improvement.For example, should Technology can be based on the progress due to sample treatment technology and sequencing technologies and feasible technology is (for example, utilize microorganism point recently Class database etc.) calculate ground generation group characterization and/or relevant recommended therapy.
Second, which can assign to processing speed, the accuracy of group characterization, the determination of microbial population associated treatment and rush Into, and/or the improvement of other suitable aspects related with illness group.For example, the technology can generate and apply feature selecting regular (for example, for compare, the microbial population drug Biodiversity Characteristics of function, pharmacogenomics etc. selection rule), with from big Measure selection optimization in potential feature (for example, can extract from a large amount of microbial population data (such as sequence data)) pond Character subset is (for example, microbial population Diversity Characteristics such as indicate the health of grouping sheet hyte relevant to illness group The reference relative abundance feature of range；The user's relative abundance feature that can be compared with reference relative abundance feature；Deng) be used for It generates and using characterization model and/or treatment model.Microbial population is (for example, human microbial group system, animal microorganism group system Deng) potential size can be converted to mass data, create the problem that how to handle and analyze mass data array with generate with The related feasible microbial population opinion of illness group.However, feature selecting rule and/or other suitable computers can be realized Rule be able to achieve shorter generation and execute the time (for example, for generating and/or application class database；For determining group Characterization and/or associated treatment；Deng), model simplification be conducive to result it is effective explanation, reduce overfitting, in data source The improvement of (for example, generate taxonomy database, etc.), identification and is presented relevant to microbial population group of illness opinion (for example, leading to Cross collect and predictive ability of relevant to the more and more users more and more data of processing to develop skill) improvement, Data storage and search (for example, relevant to the user and/or user's set particular model of storage, microorganism sequence, feature and/ Or other suitable data are to improve personalized characterization and/or delivering for the treatment of etc. for being directed to illness group) improvement and other conjunctions The suitable quickly determining improvement to promote characterization and/or treat.
Third, the technology can convert entity (for example, user, biological sample, treatment system including Medical Devices etc.) At different state or things.For example, the technology can convert biological sample to the group characterization of various diseases.In another example In, system 200 and/or method 100 can determine that treatment with promote patient change microbial population form, microbial function it is various Property, microbial population pharmacogenomics spectrum and/or other microbial population related fields to prevent and/or improve illness group One or more of illnesss, to change the microbial population and/or health of patient.In another example, the technology energy (for example, by fragmentation, multiplex amplification, sequencing etc.) microbial population data will be converted into from the received biological sample of patient Collection, can then be translated into feature relevant to illness group.For generation group characterization model and/or treatment model.? In another embodiment, which can control treatment system to promote treatment (for example, being held by generating for treatment system Capable control instruction), thus convert treatment system.In another example, the improvement of computer-related technologies can push biology The transformation of sample treatment (the primer subset for such as selecting hereditary target relevant to illness group compatible).
4th, it is including that taxonomy database, sample processing system, group characterization system and multiple users exist which, which is able to achieve, Functional creative distribution in interior network, wherein sample processing system can handle the biological sample from multiple users simultaneously (for example, in a multiplexed manner) can generate personalized characterization for illness group and/or control together with taxonomy database It treats (for example, being directed to microbial population (dietary behavior of such as user, probiotics corelation behaviour, the medical history, demographics of user , other behaviors, preference etc.) customization) in by group characterization a system utilize.
5th, the technology can improve at least with microbial population digital medical, general digital medication (digital Medicine generally), the technology neck of the computation modeling of gene sequencing and/or the related illness group of other related fieldss Domain.6th, which can be using dedicated computing equipment (for example, with sample processing system (such as sequenator system；Group characterization system System；Treatment system etc.) relevant equipment) microorganism for the treatment of determined and handled for the characterization to illness group and/or determined Group is data set.However, the case where using the non-universal computer system for group characterization and/or microbial population adjusting Under, which can provide any other suitable benefit.
3.1, system-taxonomy database
The taxonomy database 205 of system 200 can be used to provide and the associated marker information of illness group, and is suitable in life It is compared at when one or more groups of characterizations with user's microbial population feature.For example, taxonomy database 205 can store with The relevant microorganism hereditary sequence of multiple taxonomical units accordingly, can relatively deposit with one or more corresponding illnesss Storage.In another example, taxonomy database 205 can store the reference of microorganism classification unit group relevant to illness group relatively Abundance range (for example, related to the health status of one or more of illnesss, related to unhealthy condition etc.) and/or other conjunctions Suitable microbial population feature refers to microbial population feature wherein can extract based on the biological sample set from user group (for example, showing one or more of illnesss of illness group；Do not show illness；Etc.).In another example, taxonomy database 205 can store user's relative abundance range (for example, for the user with unknown micropopulation pedigree related with illness group； Deng) and/or other suitable user's microbial population features.
Taxonomy database 205 preferably stores the marker including any one in following item or more: genetic sequence (for example, the sequence of identification grouping sheet hyte；Microorganism sequence；Human sequence；Indicate the sequence of the illness from illness group；Micro- Constant sequence in biological classification unit group set and/or user；Conserved sequence；Sequence including mutation；Including polymorphism Sequence；Etc.)；Peptide sequence；Target；Feature is (for example, microbial population Diversity Characteristics, microbial population are vdiverse in function Property feature, microbial population pharmacogenomics feature etc.)；Protein types (for example, serum proteins, antibody etc.)；Carbon water Type of compounds；Lipid type；Full cell sign object；Metabolic markers；Natural products marker；Inheritance susceptible biological marker Object；Diagnostic biomarkers；Prognosis biomarker；Predict biomarker；Other Molecular biomarkers；Gene expression mark Will object；Imaging biological marker；Label corresponding to function relevant to microorganism, structure, evolution and/or other suitable characteristics Object；And/or other suitable landmarks objects relevant to microorganism (for example, taxonomical unit) and/or associated disease.By taxonomy database The genetic sequence of 205 storages preferably includes one or more gene sequences of rRNA (for example, variable region of rRNA gene order) Column, may include any one or more in lower item: 16S, 18S, 30S, 40S, 50S, 60S, 5S, 23S, 5.8S, 28S, 70S, 80S and/or any other suitable rRNA.Additionally or alternatively, genetic sequence may include following item and/or with other Mode is related to following item: other rna genes, protein gene, other RNA sequences, DNA sequence dna and/or any other is suitable Genetic aspect.The preferably shared marker feature of unlike signal object stored by taxonomy database 205, can include following item One of or more: conservative genetic sequence across multiple taxonomical units (e.g., including the semi-conservative hereditary sequence of variable region Column；The conserved sequence of the primer targeting for targeting multiple taxonomical unit races relevant to illness group can be passed through；Deng), conservative peptide Sequence, shared biomarker and/or any other suitable marker relevant information.
Stored marker is preferably related to multiple taxonomical units, so as to based on stored marker Compare and user's microorganism sequence (for example, the biological sample etc. for being originated from the collection of user) is mapped to specific taxonomical unit (example Such as, compare user's microorganism sequence and stored label to find the matching for meeting predetermined condition；Identification and matched marker Relevant taxonomical unit；And it is taxonomical unit is related to user's microorganism sequence；Deng).With taxonomy database 205, illness group (for example, alimentary canal associated disease), other systems component and/or the grouping sheet related with any part of method 100 of system 200 Hyte can include one or more of following item: clostridium (Clostridium) (category), clostridium difficile (Clostridium Difficile) (kind), another branch bacterium (Alistipes) (category), quasi- Prey irrigate bacterium (Alloprevotella) (category), anaerobism thin bar Bacterium (Anaerofilum) (category), bacteroid (Bacteroides) (category), Barnesiella (category), Bifidobacterium (Bifidobacterium) (category), Blautia (category), butyric acid vibrios (Butyricimonas) (category), campylobacter (Campylobacter) (category), Catenibacterium (category), Christensenella (category), Collinsella (category), Fecal bacteria (Coprococcus) (category), dialister bacterium (Dialister) (category), Iger hereby Salmonella (Eggerthella) (category), Angstrom Xi Shi bacillus dysenteriae (Escherichia-Shigella) (category), bacillus faecalis (Faecalibacterium) (category), Flavonifractor (category), Fusobacterium (Fusobacterium) (category), Gelria (category), haemophilus (Haemophilus) (category), Holdemania (category), lactobacillus (Lactobacillus) (category), Odoribacter (category), quiver bacillus (Oscillibacter) (category), the spirillum that quivers (Oscillospira) (category), Parabacteroides (category), Paraprevotella (category), Peptoclostridium (category), koala bacillus (Phascolarctobacterium) (category), General Salmonella (Prevotella) (category), Pseudoflavonifractor (category), Ross Salmonella (Roseburia) (category), cud Coccus (Ruminococcus) (category), salmonella (Salmonella) (category), streptococcus (Streptococcus) (category), Turicibacter (category), Tyzzerella (category), Veillonella (Veillonella) (category), Acetobacter Nitrogenifigens (kind), Acinetobacter bauamnnii (Acinetobacter baumannii) (kind), Ackermam Salmonella (Akkermansia muciniphila) (kind), Anaerotruncus colihominis (kind), Azospirillum brasilense (Azospirillum brasilense) (kind), Bacillus cercus (Bacillus cereus) (kind), bacillus coagulans (Bacillus coagulans) (kind), bacillus licheniformis (Bacillus licheniformis) (kind), bacteroides fragilis (Bacteroides fragilis) (kind), bacteroides vulgatus (Bacteroides vulgatus) (kind), bifidobacterium longum It is (Bifidobacterium longum) (kind), animal bifidobacteria (Bifidobacterium animalis) (kind), not tally Bifidobacterium (Bifidobacterium bifidum) (kind), bacillus laterosporus (Brevibacillus Laterosporus) (kind), Butyrivibrio crossotus (Butyrivibrio crossotus) (kind), campylobacter jejuni (Campylobacter jejuni) (kind), campylobacter coli (Campylobacter coli) (kind), Black-Headed Gull bent stick Bacterium (Campylobacter lari) (kind), the stick-like bacillus in Michigan (Clavibacter michiganensis) (kind), butyric acid Clostridium (Clostridium butyricum) (kind) produces gas Collins bacterium (Collinsella aerofaciens) (kind), rule Then fecal bacteria (Coprococcus eutactus) (kind), Desulfovibrio piger (kind), Dialister invisus It is (kind), italic enterococcus (Enterococcus italicus) (kind), Escherichia coli (Escherichia coli) (kind), big Enterobacteria O157 (Escherichia coli O157) (kind), pula clostridium (Faecalibacterium prausnitzii) (kind) produces succinic acid filiform bacillus (Fibrobacter succinogenes) (kind), thermophilic cock Salmonella (Kocuria Rhizophila) (kind), Lactobacillus brevis (Lactobacillus brevis) (kind), Lactobacillus coryniformis (Lactobacillus Coryniformis) (kind), bacillus acidificans longissimus (Lactobacillus delbrueckii) (kind), acidified milk bar Bacterium (Lactobacillus fermentum) (kind), opens phenanthrene at Lactobacillus helveticus (Lactobacillus helveticus) (kind) That matrix lactobacillus (Lactobacillus kefiranofaciens) (kind), Lactobacillus kunkeei (kind), mouse Lee's sugar lactobacillus (Lactobacillus rhamnosus) (kind), Lactobacillus salivarius (Lactobacillus salivarius) (kind), Fijian galactococcus (Lactococcus fujiensis) (kind), Lactococcus garvieae (Lactococcus garvieae) (kind), Lactococcus lactis (Lactococcus lactis) (kind), Leptotrichia hofstadii (kind), Leuconostoc fallax (kind), pickles leukonid (Leuconostoc kimchii) (kind), Smith's methagen (Methanobrevibacter smithii) (kind), Oneococcus onei (Oenococcus oeni) (kind) produce oxalobacter formigenes bar Bacterium (Oxalobacter formigenes) (kind), bee are like bacillus (Paenibacillus apiarius) (kind), pentose Piece coccus (Pediococcus pentosaceus) (kind), Peptoclostridium difficile (kind), Fei Shi propionic acid bar Bacterium (Propionibacterium freudenreichii) (kind), the stick-like bacillus (Pseudoclavibacter of greenish yellow vacation Helvolus) (kind), salmon Renibacterium (Renibacterium salmoninarum) (kind), Ruminococcus albus (Ruminococcus albus) (kind), ruminococcus flavefaciens (Ruminococcus flavefaciens) (kind), Bu Shi cud Coccus (Ruminococcus bromii) (kind), Ruminococcus gnavus (Ruminococcus gnavus) (kind), Bang Geersha Door Salmonella (Salmonella bongori) (kind), Salmonella enteritidis (Salmonella enterica) (kind), Bo Yideshi Shigella (Shigella boydii) (kind), Shigella sonnei (Shigella sonnei) (kind), shigella flexneri (Shigella flexneri) (kind), shigella dysenteriae (Shigella dysenteriae) (kind), Staphylococcus sciuri (Staphylococcus sciuri) (kind), Streptococcus sanguis (Streptococcus sanguinis) (kind), streptococcus thermophilus (Streptococcus thermophilus) (kind), comma bacillus (Vibrio cholerae) (kind), South Korea Wei Si Salmonella (Weissella koreensis) (kind), yersinia enterocolitica (Yersinia enterocolitica) (kind), and/ Or any other suitable marker relevant information (for example, taxonomical unit).Additionally or alternatively, grouping sheet hyte can include Any content described in the U. S. application No.14/919,614 that on October 21st, 2015 submits.For example, with above-mentioned multiple classification One or more markers relatively stored in unit can include 16S rRNA heredity relevant to multiple taxonomical units Sequence.Marker and/or multiple taxonomical units can be one or more of related (for example, being positively correlated, negatively correlated to following item Deng): illness, pathogen, symbiotic bacteria, probiotic bacteria and/or any other marker relevant information.
In modification, 205 energy storage mark object of taxonomy database is (for example, microorganism sequence, abundance feature are (such as opposite Abundance range), microbial population Diversity Characteristics, microbial population functional diversity feature, other features etc.), it is related Grouping sheet hyte and/or other data (and/or other suitable microorganism therapies related theretos) suitably related with probiotics. As such, taxonomy database 205 can improve the storage and/or retrieval of probiotics related data, it is related with probiotics for characterizing Microorganism (such as sorting group present in probiotics) and/or associated disease (for example, alimentary canal associated disease group and/or other Suitable illness etc.) relevant user's microbial population.The food source of probiotics can include: milk (such as raw milk), open Fei Er, cheese (for example, goat cheese), cocoa, pickles, Yoghourt, Kang Pucha, sauerkraut, bee product, pickles, natto, pickles, Fermented food (for example, ferment sausage), other probiotic foods, Probiotic supplement are (for example, probiotics ball, business probiotics Deng) and/or other suitable types probiotics.
As shown in Figure 11-12 and 13A-13B, with probiotics, illness, other systems component and/or system 200 and method The relevant grouping sheet hyte of 100 any part can include one or more in following item: bacillus coagulans (Bacillus Coagulans) (kind), animal bifidobacteria (Bifidobacterium animalis) (kind), clostridium butyricum (Clostridium butyricum) (kind), Lactobacillus brevis (Lactobacillus brevis) (kind), Lactobacillus coryniformis (Lactobacillus coryniformis) (kind), lactobacillus fermenti (Lactobacillus fermentum) (kind), Switzerland Lactobacillus (Lactobacillus helveticus), Lactobacillus rhamnosus (Lactobacillus rhamnosus) (kind), saliva Liquid streptococcus (Streptococcus salivarius) (kind), Acetobacter nitrogenifigens (kind), Brazil are solid Nitrogen spirillum (Azospirillum brasilense) (kind), bacillus licheniformis (Bacillus licheniformis) (kind), Bifidobacterium bifidum (Bifidobacterium bifidum) (kind), bacillus laterosporus (Brevibacillus Laterosporus) (kind), the stick-like bacillus in Michigan (Clavibacter michiganensis) (kind), italic enterococcus (Enterococcus italicus) (kind) thermophilic cock Salmonella (Kocuria rhizophila) (kind), wears ear Bu Lvkeshi Lactobacillus (Lactobacillus delbrueckii) (kind), Kefir grains matrix lactobacillus (Lactobacillus Kefiranofaciens) (kind), Lactobacillus kunkeei (kind), Lactobacillus salivarius (Lactobacillus Salivarius) (kind), Lactococcus garvieae (Lactococcus garvieae) (kind), Lactococcus lactis (Lactococcus Lactis) (kind), Leptotrichia hofstadii (kind), Leuconostoc fallax (kind), pickles leukonid (Leuconostoc kimchii) (kind), Oneococcus onei (Oenococcus oeni) (kind), bee are like bacillus (Paenibacillus apiarius) (kind), Pediococcus pentosaceus (Pediococcus pentosaceus) (kind), Fei Shi propionic acid Bacillus (Propionibacterium freudenreichii) (kind), the stick-like bacillus (Pseudoclavibacter of greenish yellow vacation Helvolus) (kind), salmon Renibacterium (Renibacterium salmoninarum) (kind), ruminococcus flavefaciens (Ruminococcus flavefaciens) (kind) Staphylococcus sciuri (Staphylococcus sciuri) (kind), stops cream Streptococcus (Streptococcus dysgalactiae) (kind), Streptococcus parauberis (kind) and South Korea Wei Si Salmonella (Weissella koreensis) (kind).In a specific example, taxonomy database 205 can include for specific Grouping sheet hyte set marker, the taxonomical unit includes bacillus coagulans (Bacillus coagulans) (kind), animal bifidobacteria (Bifidobacterium animalis) (kind), clostridium butyricum (Clostridium Butyricum) (kind), Lactobacillus brevis (Lactobacillus brevis) (kind), Lactobacillus coryniformis (Lactobacillus Coryniformis) (kind), lactobacillus fermenti (Lactobacillus fermentum) (kind), Lactobacillus helveticus (Lactobacillus helveticus), Lactobacillus rhamnosus (Lactobacillus rhamnosus) (kind), saliva hammer Bacterium (Streptococcus salivarius) (kind), wherein marker is (for example, for specific grouping sheet hyte set, use In any suitable grouping sheet hyte set etc.) group of the probiotics in relation to microorganism related with corresponding probiotics can generated (for example, as shown in figs. 14-15) is utilized in characterization (for example, composition characterization, functional diversity characterization).Relevant to probiotics In the particular instance of the grouping sheet hyte of characterization, can include, for Pediococcus pentosaceus (Pediococcus pentosaceus) The grouping sheet hyte of (kind): it is found in raw milk, pickles (kimchi), sauerkraut (sauerkraut), pickles；It is spherical； 0.5-1.0 microns of size；Without sporogenesis；It does not move；Atrichia；G+；Lactate producer；Starting culture as different fermentations Object；And/or other suitable features.In another specific example, it can be characterized using taxonomy database related with set of disorders Specific grouping sheet hyte set and/or other suitable grouping sheet hyte set, such as based on IBS inverse correlation, with 2 The inverse correlation of patients with type Ⅰ DM, inverse correlation, the inverse correlation and weight of respiratory infections duration with fat inverse correlation and IBD Mitigate it is related, and/or to any suitable related (for example, inverse correlation, the positive correlation etc.) of any suitable illness.However, point Class database 205 can be applied to probiotics in any suitable manner.
Can be generated by each section (for example, frame S110) of execution method 100 for store, retrieve, determine and/or with The taxonomy database 205 of other modes application.For example, taxonomy database 205 can include with reference to relative abundance range set (and/ Or other suitably refer to microbial population feature), it derives from: determining and illness group (for example, alimentary canal associated disease etc.) The target set of relevant taxonomical unit determines reference mark object set；And it is based on reference mark object set and taxonomical unit Target set between comparison determine selected taxonomical unit set reference relative abundance range set.Determine reference Marker set (and/or other refer to microbial population feature) can include based on from based on shared across multiple grouping sheet hytes Marker feature selection primer set prediction read determine reference mark object set (for example, sample treatment can be improved Efficiency is to promote a group characterization, wherein the primer of same or similar type can be used for targeting multiple taxonomical units relevant to illness group The marker etc. of group), wherein the comparison between reference mark object set and the target set of taxonomical unit can include the reading of prediction Sequence similarity with reference between microorganism sequence several and relevant to the target set of taxonomical unit.
3.2, system-processing system
The processing system 210 of system 200 can be used for receiving and handling (for example, fragmentation, amplification, sequencing etc.) biological sample Product.Processing system 210 can be additionally or alternatively used for Multiple users' (for example, response for the purchase order of sample reagent box 250) provide and/or collect 250 (example of sample reagent box Such as, including being configured to receive the container of biomaterial, instructing illustrating for self sampling process to user).In some realities In example, sample reagent box 250 can include material and related description for user to collect from one or more collection positions Sample by cotton swab (for example, swabbed；Fluid suction；Biopsy etc.).Collecting position can be with following one or more of phase Close: female sex organs, male sex organ, rectum, alimentary canal (gut), skin, oral cavity, nose, any mucous membrane and/or it is any its His suitable sample provide position (for example, blood, sweat, urine, excrement, sperm, vaginal fluid, tears, tissue sample, Interstitial fluid, other body fluid etc.), any of them individual sites or part combination can be with any suitable taxonomical units as described herein Group and/or associated disease are related.Processing system 210 can additionally or alternatively include library preparation system and/or any suitable Component, the library preparation system can operate with prepare automatically biological sample (for example, using with antibiotic associated disease phase The compatible primer of the nucleic acid sequence of pass carries out fragmentation and/or amplification (with multiple form etc.)) by sequencing system (example Such as, next-generation microarray dataset) sequencing.In another example, processing system 210 can be operated with based on using drawing for primer sets Object expands the nucleic acid from biomaterial to determine microorganism sequence data set (for example, by executing frame S110 and/or method The selection of 100 other desired parts etc.), wherein primer targeting corresponds to (and/or one or more of prebiotic with illness group Bacterium) the relevant taxonomical unit of one or more of illnesss microorganism sequence.In modification, processing system 210 can be with any Mode configures and/or includes that any mode similar with the U. S. application No.14/919,614 that on October 21st, 2015 submits is retouched The component (for example, sequencing system) stated.However, processing system 210 and associated component can configure in any suitable manner.
3.3, system-group characterizes system
The group characterization system 220 of system 200 can be used to determine and/or analyze to be controlled for the characterization of illness group and/or determination The microbial population data set and/or supplementary data set (for example, each section etc. for passing through execution method 100) for the treatment of.Become at one In type, the rule that group characterization system 220 can obtain and/or appliance computer executes is (for example, 205 create-rule of taxonomy database； Feature selecting rule；Model create-rule；User preference rule；Data storage, retrieval and/or display rule；Microorganism sequence Create-rule；Sequence alignment rule；And/or any other suitable rule).However, microbial population characterization system 220 can be with Any suitable way configuration.
3.4, system-treatment system
The treatment system 230 of system 200 is for promoting to user (for example, human experimenter；The nursing provided conducive to treatment Supplier etc.) one or more of treatments, to treat one or more of illnesss of illness group (for example, reducing illness Risk；Improve condition；Improve other suitable aspects of symptom and/or illness；By the microbial population drug gene of user Group is learned spectrum and is changed into vulnerable to the state with treatment for diseases, etc.).Treatment system 230 can include any one or more in following item Kind: communication system (for example, by notifying caregiver to convey treatment recommendations (such as by interface 240), with recommend and/ Or provide treatment；It being capable of tele-medicine；Deng), the application that can execute on a user device is (for example, for promoting alimentary canal related The intestinal disorder group application for the treatment of for diseases；Drug reminder application；The application journey that can be operatively communicated with automatic drug distributor Sequence etc.), consumables treatment (such as probiotic supplemented (such as includes type, dosage, treatment plan, the quantity of taxonomical unit and class Type etc.), probiotic food, antibiotic (e.g., type, dosage, medication plan etc.)), auxiliary medical equipment (for example, drug distribute Device；Antibiotic medication device etc.), user equipment (e.g., including biometric sensor) and/or any other is suitable Component.In an example, treatment system 230 can operate the supply to promote consumables treatment based on group characterization, wherein Consumables treatment can be operated to influence user's microbial population group relevant to illness (for example, the alimentary canal associated disease etc.) At at least one of with microbial population function, and promote the improvement of state of an illness state.In a specific example, treatment can be wrapped Include the related treatment of probiotics for the illness, wherein probiotics it is related treat and taxonomical unit set (e.g., including this paper institute Grouping sheet hyte stated etc.) it is related, and wherein treatment system 230 includes for promoting the classification from the taxonomical unit set The relevant interface 240 of unit group therapy related to probiotics.One or more treatment systems 230 preferably can be by a group characterization system 220 control of system.For example, group, which characterizes system 220, can generate control instruction and/or notice to be sent to treatment system 230 to activate And/or operate treatment system 230 otherwise to promote to treat.However, treatment system 230 can match in any other manner It sets.
3.5, system-interface
As shown in figs. 14-15, system 200 can additionally or alternatively include interface 240, interface 240 can be used to improve with Such as group characterization, associated treatment suggestion, the ratio compared with other users, based on demography and/or other user characteristics Compared with, microbial population Diversity, microbial population functional diversity, microbial population pharmacogenomics and/or other Suitable aspect related group of characterization information, probiotics are for information about and/or other suitable microorganism groups are the aobvious of relevant information Show.In another example, 240 energy presentation group characterization information of interface, including microbial population composition is (for example, grouping sheet hyte Relative abundance), functional diversity (for example, relative abundance of gene and/or it is other it is relevant to function characterization etc.), and/or For other appropriate informations (for example, composition related with illness group) of illness group.In another example, organize characterization information, Probiotics is for information about and/or other appropriate informations can be rendered as a sharing feature (for example, similar diet behavior, similar people Mouthful statistics feature, the patient of shared illness, smoker, person taking exercise, the user of different diet programs, probiotics consumer, Antibiotic user, the group for carrying out specific treatment etc.) user's subgroup.
In another example, interface 240 can be operated so that antibiotic is presented for information about, including with treatment and antibiotic The related microbial population pharmacogenomics spectrum of associated disease (and/or microbial population composition, microbial population are vdiverse in function Property etc.) change with time.In a specific example, interface 240 can be operated to improve and can treat illness phase with antibiotic The antibiotic-related information of pass, and user's microbial population based on user relative to the user group of shared Demographic Comparison between pharmacogenomics spectrum and the display of relevant information obtained.In another specific example, interface 240 can promote Into (for example, present, notice is provided etc.) with from the taxonomical unit set (for example, recommendation includes related with the illness of illness group Taxonomical unit microorganism probiotics etc.) grouping sheet hyte relatively treat (for example, the related therapy of probiotics).Another It, can be by selection (for example, the component based on the group characterization for meeting threshold condition in one specific example；To be more than threshold value it is similar The micropopulation pedigree of the matched user of reference spectrum of property；More than the risk of the illness group of threshold value；Other trigger events etc.) and it is micro- The presentation (for example, the subclass for highlighting and/or otherwise emphasizing information) of biotic formation relevant information subclass comes Improve the interface display of microbial population relevant information.However, interface 240 can show any suitable information and can be with any Suitable mode configures.
The component of system 200 and/or system 200 can completely or partially by the execution of following item, trustship (host on), with Following item communication and/or including following item: remote computing system is (for example, server, at least one networked computing system, ill-mannered (stateless) of state, stateful (stateful)), local computer system, database (for example, taxonomy database 205, use User data library, microbial population data set database, illness group database, treatment data library etc.), user equipment is (for example, user Smart phone, computer, laptop, auxiliary medical equipment, wearable Medical Devices, caregiver's equipment etc.) and/or Any suitable component.For example, system 200 can include computing system, can operate with processing system 210 (for example, processing The next-generation microarray dataset of system 210) it communicates to execute the desired part of method 100 (such as to determine that microbial population drug base Because of a group data).Although the component of system 200 is generally described as different components, they can physics in any way It ground and/or logically assembles.For example, smart mobile phone application can partially or completely execution group characterization system 220 (for example, answering Such as generate the group characterization of illness group in real time with group characterization model；Biological sample is sequenced；Handle microorganism sequence；From microorganism Group is that feature etc. is extracted in data acquisition system) and treatment system 230 (for example, being communicated with the calendar applications of smart phone to lead to Know user and take probiotics etc. according to the parameter determined by probiotics agents treatment model).Additionally or alternatively, system 200 Functionality can be also distributed in any suitable manner between any suitable system component.However, the component of system 200 can be with Any suitable way configuration.
4, method
As shown in Figure 1A -1B and 2, for characterizing illness group (for example, alimentary canal related diseases based on processing biological sample Disease) the embodiment of method 100 can include: to generate taxonomy database S110 relevant to the marker of multiple taxonomical units； Based on the biological sample collected from user, be generated for user microbial population data set (e.g., including micro- life of microorganism sequence Object sequence data collection etc.) S120；And/or based on taxonomy database and microbial population data set (and/or supplementary data set and/ Or other suitable data), to microbial population composition, microbial population functional diversity and/or associated disease (for example, really Determine illness group group characterization) at least one of execute characterization process S130.Method 100 can additionally or alternatively include: to receive Collect the supplementary data set S125 of illness group；Promote the treatment S140 of user based on characterization process；Determine the related characterization of probiotics S145；Proof list is gone on a punitive expedition journey S150；And/or any other suitable process.
In modification, the frame of method 100 can repeat the refining to realize taxonomy database in any suitable order (for example, by identifying new marker relevant to different taxonomical unit and/or illness etc.), refining characterization process is (for example, logical The relative abundance for updating and comparing ownership goal with reference to abundance is crossed, to identify clinically relevant result；By generating and updating characterization Model；The illness quantity of single creature sample characterization can be used by increasing；Deng), therapeutic process is (for example, by any time Treatment monitoring and adjusting microbial population composition, such as by being iteratively performed frame S120 and S130 at any time, wherein can be based on Characterization result with sensitivity, specificity, accuracy and negative predictive value selects to treat；Deng) and/or other suitable mistakes Journey.
One or more examples of method described herein 100 and/or process can pass through and/or using described herein System (e.g., including sample treatment network, group characterization system, treatment system, sample reagent box etc.), element and/or entity One or more examples not simultaneously (for example, sequentially), simultaneously (for example, concurrently；Multiplexing is to realize parallel processing Multiple biological samples；Different syndromes are characterized with calculating simultaneously on the different threads for parallel computation to improve system processing energy Power；Deng), with the time relationship of trigger event, and/or suitably sequentially held with any other in any suitable time and frequency Row.
Additionally or alternatively, data described herein are (for example, microorganism sequence data, microbial population feature, such as Group characterization and/or probiotics characterization, population level data in relation to characterization；User's horizontal data；Treat related data；Deng) energy Be with any suitable time indicator (for example, the second, point, hour, day, week etc.；Time indicator is indicated when to collect, be determined And/or otherwise handle data；Time indicator provides the context of the content described by data, such as refers to as the time Show the state of illness group when biological sample is collected in symbol instruction；Deng) and/or time indicator variation (for example, microbial population Feature changes with time；Microbial population Diversity, functional diversity and/or other suitable aspects are with the time Variation；The variation of data；Data pattern；Data trend；Data Extrapolation and/or other predictions；Deng) related.However, this method energy It executes in any suitable manner.
4.1, method-generation taxonomy database
Frame S110 is recorded: one or more taxonomy databases relevant to the marker of multiple taxonomical units are generated, It can be used for creating database, which includes being suitable for carrying out when generating one or more characterizations with user's microorganism sequence The marker information compared.
Generate taxonomy database S110 preferably include determine for taxonomy database reference mark object set (for example, The prediction reading of primer based on the shared marker feature selection being originated from based on multiple taxonomical units；Deng)；Determine taxonomical unit Target list (for example, related to alimentary canal associated disease)；Based on comparison (for example, compared with sequence) mistake with reference mark object Filter the target list (for example, while using Optimal Parameters) of taxonomical unit；And in taxonomy database, store and corresponding The relevant filtering of reference mark object taxonomical unit (for example, as shown in figs. 9 a-9b).
About frame S110, one or more of primers are preferably based on (for example, for expanding the hereditary object for carrying out biological sample The primer of matter, as described in frame S120 etc.) determine reference mark object set.For example, frame S110 can include: to be expanded based on primer prediction Increase son (for example, for positive V4 primer GTGCCAGCMGCCGCGGTAA and for reversed GGACTACHVGGGTWTCTAAT Deng), the annealing (for example, most 2 mispairing in entire sequence) for making it possible to meet threshold condition carrys out self-reference for comparing The sequence (for example, SILVA database) of database；It (is expanded to for example, filtering out more than 20 kinds based on degeneracy filtering amplicon The degeneracy amplicon of possible nondegenerate sequence)；Modify filtered amplicon with indicate positive reading (e.g., including it is positive Primer and 125bp etc. to the end 3' of forward primer) and back readig (e.g., including reverse primer and to reverse primer The 124bp etc. of the end 3')；Handle modified amplicon (for example, removing primer)；And store the place as reference mark object The amplicon managed is (for example, the 125bp after forward read is plus the 124bp after reverse read；Type of attachment；Etc.).In addition Or alternatively, amplicon prediction, processing and/or relevant operation can be based on any suitable primer, and/or can be with any suitable Mode configure to determine reference mark object.
About frame S110, determine the target list of taxonomical unit (for example, category relevant to set of disorders set and kind set Deng) the related information source of processing illness is preferably included (for example, third party's information source, scientific literature, clinical test etc.； Source including the information about illness, related microorganisms and/or Research of predicting markers etc.).In modification, frame S110 can include hand It is dynamic to handle illness related information source (for example, marker and/or the labor management of relevant information etc.) to generate the target of taxonomical unit Mark list.In another modification, frame S110 can include automatically processing the relevant information source of illness.For example, frame S110 can include: Generate the list of online information source；Online information source is obtained based on list；Online information source is handled to extract for generating grouping sheet The taxonomical unit set of the target list of position, associated disease and/or other related datas are (for example, by using at natural language Reason technology etc.).
Determine the target list of taxonomical unit preferably include based on compared with reference mark object set come filtering classification The target list of unit.For example, frame S110 can include self-reference in future marker set reference mark object with come from grouping sheet The taxonomical unit of the target list of position is related, such as based on relative to reference mark object set use from multiple grouping sheets The length of the related gene sequence of one or more taxonomical units of position (for example, region 16S rRNA gene V4 of taxonomical unit) 100% 100% identity, carry out sequence similarity search.However, any suitable identity parameter, length parameter and/ Or other suitable parameters can apply to sequence similarity search, and can be in any suitable manner by reference marker and classification Unit is related.Preferably, according to Optimal Parameters (for example, optimization sensitivity, specificity, accuracy, negative predictive value and/or its He measures (by using confusion matrix) etc.) come filter preliminary target list Different groups reference mark object.One In a example, as shown in Fig. 6 and 9A-9B, can based on Optimal Parameters threshold value (such as, it is desirable that each Optimal Parameters are more than 90%；It wants Refinement degree is more than 95%；Etc.) filter the taxonomical unit from preliminary target list.In another example, frame S120 can be wrapped It includes: generating given taxonomical unit multiple subdata bases relevant to reference mark object (for example, the sequence) of different number, thus Generate different Optimal Parameters spectrums.In a specific example, frame S110 can include: the received clearly corresponding to taxonomical unit One reference mark object subset；It is ranked up based on reference mark object of the quotient of dt/ti to the second subset from reference mark object, Wherein " ti " indicates the annotation to the sequence of interested taxonomical unit, and " dt " is indicated to the sequence of different taxonomical units Annotation；It is that taxonomical unit generates subdata base set (for example, based on 0 quotient's condition optimizing specificity based on different quotient's conditions Subdata base；Optimize the subdata base for identifying true positives based on quotient's condition 100)；Determine the excellent of the subdata base set Change parameter sets；Based on the subdata base of the taxonomical unit corresponding to the Optimal Parameters for meeting Optimal Parameters threshold value, filtering classification The preliminary target list of unit；And filtered taxonomical unit relevant to corresponding reference mark object is stored in classification data In library.Additionally or alternatively, determine that the target list of taxonomical unit can execute in any suitable manner.
About frame S110, additionally or alternatively, generating taxonomy database can include based on processing and received from user group The supplementary data set of body is relevant to identify reference mark object and associated taxon (example from the received biological sample of user group Such as, microbial population composition characteristic and/or microbial population functional diversity based on the biological sample for originating from user's collection Feature determines the correlation for the illness reported with user itself), but determine the reference mark object for corresponding to target taxonomical unit It can execute in any suitable manner.However, generating taxonomy database can execute in any suitable manner.
4.2, method-generation microbial population data set
Frame S120 is recorded: being one or more users (for example, being used for based on the biological sample collected from multiple users Determine the current subject of group characterization；For generating the subject group of taxonomy database；Deng) generate one or more micro- lifes Object group is data set (e.g., including microorganism sequence data set of microorganism sequence etc.).Frame S120 is received for handling from user The biological sample of collection, so as to can be followed by subsequent processing based on taxonomy database determination microorganism sequence (for example, execute microorganism sequence And the sequence being stored between the genetic sequence in taxonomy database compares) to determine that user characterizes.
Frame S120 can include any one in following item or more: cracking biological sample (such as be used in combination and stablize Buffer etc.), destroy biological sample cell membrane, unexpected component (for example, RNA, protein) is separated from biological sample Nucleic acid in (for example, extracting microbial DNA etc. using the method based on column using liquid handling robot), purifying biological sample (for example, DNA), amplification (for example, utilizing library preparation system) come the nucleic acid of biological sample, biological sample is further purified The nucleic acid of the amplification of the nucleic acid, biological sample of amplification is sequenced (for example, to end schema creation 2 on NextSeq platform × 150bp a pair of end sequence；Etc.) and/or any other suitable sample treatment operation, such as about December 9 in 2016 The U. S. application No.15/374 submitted day, operation, entire contents are incorporated herein by reference those of described in 890.
In the modification of frame S120, the amplification of purified nucleic acid can include carrying out one of following item or more: Technology based on polymerase chain reaction (PCR) is (for example, Solid phase PCR, RT-PCR, qPCR, multiplex PCR, landing-type PCR, nanometer PCR, nest-type PRC, heat start PCR etc.), helicase dependent amplification (HDA), ring mediate isothermal duplication (LAMP), from main sequence Column duplication (3SR), the amplification (NASBA) based on nucleic acid sequence, strand displacement amplification (SDA), rolling circle amplification (RCA), ligase chain Formula reacts (LCR) and/or any other suitable amplification technique.When expanding purified nucleic acid, primer used is preferably It is selected as preventing or minimizing amplification deviation, and/or is configured to expand relevant to the marker stored in taxonomy database (for example, in frame S130, amplification can be with biology point for nucleic acid region/sequence (for example, the region 16S, the region 18S, the region ITS etc.) The gene order that marker in class database is compared；Amplification corresponds to the genetic sequence of marker feature；Amplification is used for Diagnosis, the genetic sequence of multi information on taxology, systematic growth for being used for preparation (such as probiotics preparation)；Deng), And/or it is configured for any other suitable purpose.
In example relevant to frame S120, it is configured to avoid the universal primer of amplification deviation (for example, for 16S RNA F27-R338 primer sets, the F515-R806 primer sets etc. for 16S RNA) for expanding.In a specific example, frame S120 may include with general V4 primer (for example, 515F:GTGCCAGCMGCCGCGGTAA and 806R: GGACTACHVGGGTWTCTAAT) and it is relevant to variable (for example, semi-conservative hypervariable region) area (for example, the region V1-V8) its Any other suitable portion of his suitable primer amplification 16S gene (for example, gene of coding 16S rRNA) and/or rna gene Point.In another example, box S120 can include selecting primer relevant to protein gene (for example, coding is across multiple points Conservative protein matter gene order of class unit etc.).In another example, in addition the primer used in frame S120 modification can be Or alternatively include the incorporation bar code sequence special to each biological sample, the mirror of biological sample after amplification can be promoted It is fixed.The primer of selection can be additionally or alternatively with illness, microbial population composition characteristic (for example, corresponding with hereditary target Identification primer, correspond to the relevant microbial population composition characteristic of grouping sheet hyte relevant to ventosity；It is originated from The genetic sequence etc. in relative abundance feature source), functional diversity feature, complementary features and/or other suitable features it is related. Primer can additionally or alternatively include adaptation area, be configured to aptamers complementary with being related to sequencing technologies (for example, Illumina sequencing) cooperation.Primer (and/or other suitable molecule, marker and/or biomaterials as described herein) can have There is any suitable size (for example, sequence length, base logarithm, conserved sequence length, variable section length etc.).In addition it or can replace Dai Di can be characterized in sample treatment using any appropriate number of primer (for example, group characterization, the related table of probiotics Sign etc.), wherein primer can be with any appropriate number of target, sequence, taxonomical unit, illness and/or other suitable aspect phases It closes.It can be by method described in any other suitable part of frame S120 and/or method 100 (for example, based on for generating The primer of the parameter of taxonomy database selects) come other suitable portions of primer used in choice box S120 and/or method 100 Point.Additionally or alternatively, primer (and/or process relevant to primer) can include and/or similar on October 21st, 2015 Described in the U. S. application No.14/919,614 of submission those.However, the identification and/or use of primer can be with any suitable Mode configure.
Related to sequence reads in modification, frame S120 can include one of following item or more: filter, trim, Additional, cluster marks (for example, as practical genetic sequence；As mistake；Deng).In a specific example, frame S120 can be wrapped It includes the amplification based on 16S gene and generates reading set；Use average Q-scores > 30 filter reads；From trimming primer in reading with before Lead base；Additional forward and reverse is read；(for example, using Swarm algorithm) is clustered using the distance of 1 nucleotide；It will Every the most abundant reading sequence mark of cluster is actual genetic sequence；For each cluster, the most abundant reading sequence is distributed, is had There is the counting of the reading corresponded in cluster；Also, for each cluster, chimera is executed to the most abundant reading sequence and removes (example Such as, using VSEARCH algorithm etc.).However, can be sequenced in any suitable manner.
For any appropriate number of biological sample, it is any suitable described in frame S120 to be executed with multiplex mode Process.In an example, frame S120 can include being carried out with forward and reverse index (for example, unique combinations) to multiple samples Barcode encoding is sequenced multiple samples with multiplex mode；Also, after sequencing, it is corresponding to be divided into multichannel process In the sample (for example, utilizing BCL2FASTQ algorithm etc.) of different user.It additionally or alternatively, can be in any suitable time Any amount of example of each section of frame S120 is executed with frequency.However, frame S120 can be to be similar to full content by drawing With the U. S. application No.15/374 submitted 9 days December in 2016 being incorporated herein, 890 any suitable way is executed, and/ Or it can execute in any suitable manner.
4.3, method-collection supplementary data set
Frame S125 is recorded: being received and is provided the supplementary data set of illness group and/or probiotics for information about.Frame S125 can be used for Additional data relevant to one or more users that user gathers is obtained, training can be used for and/or is verified in frame S130 Therapeutic process (for example, treatment model) in the characterization process (for example, characterization model) of middle generation, frame S140 and/or it is any its His suitable process.Supplementary data set preferably includes the data that investigation obtains, but can additionally or alternatively include following Any one of or more: diagnosis related data is (for example, chylous diarrhea test, colonoscopy, sigmoidoscopy Look into, lower gastrointestinal tract photography, upper gastrointestinal tract endoscopy, upper gastrointestinal tract photography, simulation colonoscopy etc.), come from sensor And/or any other appropriate component (may include therapeutic equipment, such as smart phone, wearable for example, the component of system 200 The user equipmenies such as Medical Devices) multi-faceted data, medical data is (for example, current and history medical data, such as antibiotic are sick History), group one or more illnesss multiple information data (for example, illness exist or lack instruction, dependent diagnostic, correlation Treatment, progress at any time etc.) and/or any other suitable type data.In the modification of frame S125, the number investigated According to physiology relevant to subject, demographics and behavioural information can be provided.Additionally or alternatively, frame S125 can with whole The U. S. application No.14/919,614 that the 21 days October in 2015 that content is incorporated herein by reference submits similar any mode It executes.However, processing supplementary data set frame S125 can be executed in any suitable manner.
4.4, method-execution characterizes process
Frame S130 is recorded: being based on taxonomy database and microbial population data set, is formed to microbial population, micropopulation It is that at least one of functional diversity and/or associated disease execute characterization process.Frame S130 can be used to handle and classification data The related microbial population data set (for example, generating in frame S120) in library (for example, generating in frame S110) is user's life At one or more characterizations.The characterization of user can include 9 days December in 2016 being incorporated herein by reference with full content The U. S. application No.15/374 of submission, those similar any characterizations are (for example, be related to the different populations of user described in 890 The relative abundance of the microbial population composition of the Different groups of statistical nature；Disease risk；The pertinent trends changed over time； Deng).
Frame S130 can include one of following item or more: determine with reference to microbial population parameter area (for example, strong Health refers to relative abundance range, and all as shown in Figure 8, wherein range can be related to the shortage of one or more illnesss；With one The presence of kind or more illness and/or the relevant risk of risk refer to abundance range；One or more taxonomical units it is rich The microorganism compositing range of degree；The Microbial functional diversity model of functional character relevant to one or more of taxonomical units It encloses；Deng)；Determine user's microbial population parameter of user；Join based on user's microbial population parameter and with reference to microbial population The comparison between range is counted to generate the characterization of user (for example, as handled unsound micropopulation relevant to general Bordetella System forms and characterizes user, general Bordetella abundance of the general Bordetella based on instruction except general Bordetella health term of reference User's microbial population parameter；Deng) and/or any other suitable operation.Can have with reference to microbial population parameter area (for example, for the relative abundance of Ruminococcus, 0%) lower limit is higher than any suitable lower and upper limit.With reference to micropopulation It is the range (for example, 99% confidence interval across user group) that parameter area can include the representative of any suitable confidence interval. In an example, it can be calculated for any suitable taxonomical unit (for example, target list from taxonomical unit) and refer to phase To abundance range, such as counted divided by total indicator reading based on the reading that will correspond to the taxonomical unit (for example, aggregated and filtering The sum of reading)；However, can be calculated in any suitable manner with reference to relative abundance range.
Frame S130 preferably includes the one kind for determining one or more illness groups (for example, alimentary canal associated disease group etc.) Or more group characterization.For one or more of illnesss of the group, group characterization can include one or more of in following item: disease The presence of disease, the shortage of illness, the risk of illness, the seriousness of illness, recommendation relevant to illness, micro- life relevant with illness Object group be composition (for example, microbial population Diversity comprising the relative abundance of taxonomical unit relevant to illness), with The relevant microbial population functional diversity of illness, microbial population pharmacogenomics relevant to illness are (for example, for disease User's pharmacogenomics of potential effect of different antibiotic of disease are composed), probiotics relevant to illness is (for example, source, related Sorting group, correlation etc.), and/or any other suitable aspect relevant to illness group.
In the modification of frame S130, it can execute and be determined with reference to microbial population parameter area by rule of thumb.For example, frame S130 energy Including collecting biological sample and supplementary data set from user group.The user group can include and microbial population forms, micro- life Object group is the relevant user of any suitable state of functional diversity, illness and/or other suitable characteristics, wherein supplementary data Collection (for example, the digital management at the application program executed in mobile device related to user is investigated) can provide multi information Feature.In an example, supplementary data set can be informed including one of following item illness or more: cancer, infection, fertilizer Fat, chronic healthy problem, mental health obstacle and/or any other suitable illness.In specific example, method 100 can be wrapped Include: biological sample of the processing from healthy user group is (for example, be never diagnosed as with hyperglycemia and/or diabetes, digestion Road related symptoms and/or the user of other illnesss etc.)；Biological sample is handled (for example, if frame S120) is to determine microorganism sequence； Determine the relative abundance (for example, target list from taxonomical unit) of each taxonomical unit of each user；And according to health The relative abundance of user group is that each taxonomical unit generates healthy range.In another specific example, method 100 can include: Determine the taxonomical unit set reference relative abundance range set include: for user group collect supplement biological sample set and The set of supplementary data set；The supplement biological sample set is handled using primer sets relevant to microorganism associated disease group to produce Raw supplement microorganism sequence data set；And reference is determined based on the set of supplement microorganism sequence data set and supplementary data set Relative abundance range set.However, being empirically determined can execute with reference to microbial population parameter area in any suitable manner. In another modification of frame S130, determine with reference to microbial population parameter area can it is non-empirically execute, such as based on manually and/ Or automatically process illness related information source.However, determine with reference to microbial population parameter area can in any suitable manner into Row.
About frame S130, determine user's microbial population parameter of user be based preferably on the biological sample from user and The microorganism sequence of generation is (for example, as in frame S120；Clustered and filtering reading；Deng).For example, determining user micropopulation It is the relative abundance that parameter can include determining different classifications unit (for example, identifying in the target list of taxonomical unit).? In further example, determine that user's microbial population parameter can include extracting feature relevant to group (for example, such as Fig. 4 institute Show), it can include one of following item or more: microbial population composition relevant to one or more of illnesss of group Feature, microbial population functional character, microbial population pharmacogenomics feature and/or other suitable features, such as with Similar to the U. S. application No.15/374 that on December 9th, 2016 submits, 890 mode, entire contents are incorporated by reference into this Text.In an example, it is user's extraction group correlated characteristic set that method 100, which can include: based on microorganism sequence data set,；Really Fixed reference feature is determined compared between the group correlated characteristic set of user；The related illness of microorganism is directed to based on relatively more determining user The group feature of group.In a specific example, method 100 can include: the relevant characteristic set of extraction group comprising be based on micro- life Object sequence data collection extract this group of correlated characteristic set microbial population Diversity Characteristics and microbial population function it is more Sample feature, and wherein determine relatively to include determining the fixed reference feature with microbial population Diversity Characteristics and having The comparison of the fixed reference feature of microbial population functional diversity feature.In a specific example, method 100 can include: from micro- The value of biotic formation composition characteristic and/or microbial population functional diversity feature is (for example, from the biological sample of healthy user Obtain etc.) determine with reference to microbial population parameter area；And by user's microbial population composition characteristic value and/or the micro- life of user Object group is functional diversity characteristic value to be compared with reference to microbial population parameter area, with determine user characterization (for example, For the illness with the positive correlation of reference microbial population parameter area and/or negative correlation).
About frame S130, by one or more user's microbial population parameters and it is one or more with feature (for example, Taxonomical unit, illness etc.) it is relevant it is one or more with reference to microbial population parameter areas be compared can include based on use Family microbial population parameter value whether fall in reference to being characterized as possessing by user inside or outside microbial population parameter area or Do not possess this feature.For example, frame S130: can include obtaining Smith's methagen (Methanobrevibacter smithii) Health refer to relative abundance range；And there is the Smith's methane for being more than health with reference to relative abundance range in response to user The relative abundance of bacillus (Methanobrevibacter smithii), characterization user are in the risk of intestinal irritable syndrome. In another example, determine that the comparison between fixed reference feature and the relevant characteristic set of group can include determining the relevant feature of group Gather related at least one of following item: the presence of microbial population composition characteristic, microbial population composition characteristic it is scarce It loses, between the relative abundance of each grouping sheet hyte of taxonomical unit set, at least two features relevant to taxonomical unit set Ratio, the systematic growth distance between interaction and grouping sheet hyte between grouping sheet hyte.In another example In, generating taxonomy database can include the reference relative abundance range set for determining the taxonomical unit set, and wherein this refers to phase It is related to abundance range set illness group related to microorganism；It is that user extracts the taxonomical unit based on microorganism sequence data set User's relative abundance range set of set；And determine this with reference to relative abundance range set and user's relative abundance range set Comparison between conjunction.In another example, determine that fixed reference feature can include executing compared between group correlated characteristic set At least one of following item: forecast analysis, multihypothesis test, random forest is examined and principal component analysis.However, comparing one A or more user's microbial population parameter can execute in any suitable manner.
Additionally or alternatively, for frame S130, executing characterization process can be based on threshold value (for example, based on being related to and the disease The relative abundance of the taxonomical unit set of the relevant sets of threshold values of disease determines the risk of illness group, etc.), weight is (for example, first point The weighting of the relative abundance of class unit is heavier than the weighting of the relative abundance of the second taxonomical unit, such as when the first taxonomical unit with When interested illness has a bigger correlation etc.), machine learning model is (for example, the microorganism stored in taxonomy database Group is the disaggregated model training and the respective labels of taxonomical unit of feature；Deng), computer implemented rule is (for example, for extracting The characteristic Design rule of microbial population feature；Model create-rule；User preference rule；Microorganism sequence create-rule；Sequence Column comparison rules；Deng) and/or any other suitable aspect.
Additionally or alternatively, for frame S130, executing characterization process can be configured as at least one measured in following item It is a: risk score, and/or significant sex index is with by taxon or taxonomical unit set and interested illness (or illness group) Similar any mode in a manner of described in the U.S.Provisional Serial 62/558,489 submitted for 14th with September in 2017 Correlation is incorporated herein by reference in their entirety.However, frame S130 can be executed in any suitable manner.
In modification, other desired parts of frame S130 and/or method 100 can include applying one or more models (for example, group characterization model；Probiotics characterization model；Treat model；Deng) comprising it is one or more in following item: general Rate attribute, heuristic attribute, certainty attribute and/or any other suitable attribute.Each model can run or update: Once；With scheduled frequency；The example of the embodiment of method and/or subprocess is executed every time；Meet trigger condition (example every time Such as, the audio active that detection audio data is concentrated；Detect speech activity；Detect unexpected measurement；Deng), and/or to appoint What his suitable temporal frequency.Module can with other one or more models simultaneously, continuously, with the frequency of variation, And/or it in any other suitable time operation or updates.It can be according to new received latest data；Historical data is based on any Each model is checked and verify, is reinforced, calibrating or otherwise updating in data verification that other suitable data are updated.In addition Or alternatively, model and/or related fields (for example, method, algorithm etc.) can with be incorporated herein by reference in their entirety The similar mode of mode described in the U. S. application No.15/374,890 that on December 9th, 2016 submits configures.However, frame S130 can be executed in any suitable manner.
4.5, method-promotion treatment
Method 100 can additionally or alternatively include frame S140, record: based on characterization process (for example, based on group table Sign is based on the related feature of probiotics, is based on feature；Deng) promote treatment.Frame S140 can be used for it is determining to user, recommend and/or Personalized treatment is provided, to adjust the microbial population of user composition and/or functional character to desired equilibrium state, And/or improve one or more of illnesss.For example, frame S140 can include based on group characterization (and/or probiotics related characterization) to User promotes probiotics consumables, and wherein probiotics consumables can be operated to improve multiple micro- lifes of microorganism associated disease group Object associated disease.In another example, method 100 can include the relevant benefit of collection diet relevant to the dietary behavior of user Data set is filled, wherein promoting probiotics consumables includes based on the relevant supplementary data set of diet and group characterization (and/or probiotics Characterize) probiotics consumables are promoted to user.
Therapy may include following any one or more: probiotics, consumables (such as varieties of food items, various types of beverages Deng), local treatment (for example, lotion, ointment, preservative etc.), nutritional supplement is (for example, vitamin, minerals, fiber, fat Acid, amino acid, prebiotics etc.), drug, antibiotic, bacteriophage and any other suitable remedy measures.It is generated in frame S130 Characterization can be used to determine and/or promote to the customization therapy of user, such as including preparation and scheme (for example, dosage, using saying It is bright).For example, method 100 can comprise determining that user of the health with reference to the taxonomical unit except relative abundance range of taxonomical unit Relative abundance；And the microbial population for promoting probiotics and/or other suitable therapies to adjust user forms, so that user's phase To abundance in health with reference within the scope of relative abundance.Therefore, frame S140 can include determining and/or being provided arranged to correction ecology The treatment of imbalance feature (for example, identified based on the characterization determined in the frame S130, etc.).
In modification, frame S140 can include determining and/or providing the treatment with one or more treatment systems, described Treatment system can include any one of following item or more: communication system is (for example, for conveying treatment recommendations；For Enable tele-medicine；Etc.), the application program that can execute on a user device is (for example, for promoting to gastral appropriate shield Reason alimentary canal associated disease application etc.), auxiliary medical equipment (for example, for alimentary canal associated disease therapeutic equipment and/or Diagnostic device, pill dispenser, probiotics distributor etc.), user equipment (e.g., including bioassay sensor) and/or appoint What his suitable component.As such, frame S140 can additionally or alternatively include generate for treatment system control instruction and/ Or notice, the treatment system are for activating and/or otherwise operating and promote treatment-related treatment system.So And executing frame S140 using treatment system can execute in any suitable manner.
In another modification, frame S140 can include generating and/or providing to user to generate about treatment, in frame S130 Feature and/or any other suitable information notice (for example, the microbial population of patient is reported, as shown in Figure 5).It is logical The mode of the type and offer notice known can be similar to what the 9 days December in 2016 that full content be incorporated herein by reference submitted Described in U. S. application No.15/374,890.However, frame S140 can be executed in any suitable manner.
4.6, method-determines the related characterization of probiotics
Method 100 can additionally or alternatively include frame S145: determine the related characterization of probiotics.Frame S145 can be used to handle The relevant microbial population data set with taxonomy database (e.g., including probiotics in taxonomy database for information about etc.) (for example, being generated in frame S120), the relevant characterization of one or more probiotics is generated for user.Additionally or alternatively Ground, frame S145 can be used to promote the related therapy of probiotics can be based on the determination of the group characterization of (for example, determine and/or promote).Such as Shown in Figure 10, frame S145 can include any one of following item or more: determine probiotics source, determination and probiotics Related grouping sheet hyte, determination and the related illness of probiotics (for example, illness group) generate description probiotics as described herein Characterization and/or other suitable information for information about determine the related feature of probiotics (for example, characterization and/or treatment can be based on Those of；Deng) and/or any other suitable process.In a specific example, frame S145 can include: the potential benefit of identification Raw bacterium；Characterization based on probiotics filters potential probiotics compared with the relevant performance metric of probiotics；Identify probiotics In relation to illness (for example, health benefits, probiotics source grouping sheet hyte relevant to probiotics)；And it is based on and probiotics Comparison in relation to illness carries out second of filtering of probiotics.In another specific example, method 100 can include: for probiotics Bacterial strain determines range (for example, relative abundance range；Healthy range etc.) (for example, can reliably be identified by analyzing performance metric, Such as by executing one or more processes being described herein)；By range (for example, term of reference) with it is one or more A illness is related；Determine the user scope of user；User scope is compared with term of reference；And/or it is determined based on comparing Treatment.Grouping sheet hyte relevant to probiotics can include any suitable grouping sheet hyte as described herein (for example, with classification Database is related etc.).However, frame S145 can be executed in any suitable manner.
4.7, method-proof list is gone on a punitive expedition journey
Method 100 can additionally or alternatively include frame S150, record: proof list is gone on a punitive expedition journey.Frame S150 can be used for base In microbial population data set and taxonomy database verifying for one or more characterizations to be generated for user (for example, such as frame In S130) used in process, so as to promote user's microbial population parameter and/or refer to microbial population parameter area (example Such as, the relative abundance of target taxonomical unit) accurate determination.Proof list is gone on a punitive expedition, and to preferably include execution related to reference sample for journey Frame S110-S140 in it is one or more (for example, have known microbial population composition and/or microbial population function Energy diversity, is related to the target list etc. of taxonomical unit).In a variant, frame S150 can include based on dilution and mesh The relevant inhereditary material of taxonomical unit is marked (for example, the inhereditary material of synthesis, such as represents the 16S of different target taxonomical units The synthetic dsdna in the region V4 of rRNA gene, such as " sDNA " in Fig. 7 are shown) (for example, with any suitable ratio) production Raw reference sample；And by execute in frame S110-S140 it is one or more handle reference sample, with verify with reference to sample The detection of the relevant target taxonomical unit of product.In another modification, frame S150 can include processing from true or synthesising biological Sample (for example, the work with known composition or recombined material fecal specimens, as shown in " verification sample " in Fig. 7；Deng) Reference sample to verify the detection of target taxonomical unit relevant to reference sample.Additionally or alternatively, frame S150 can be wrapped Include based on proof list go on a punitive expedition journey result come modify to it is one or more relevant one or more in frame S110-S140 Parameter.However, frame S150 can be executed in any suitable manner.
The system of method 100 and/or embodiment is at least partly presented as and/or is embodied as being configured as receiving depositing Store up the machine of the computer-readable medium of computer-readable instruction.These instruction can by with application, small routine, host, server, Network, website, communication service, communication interface, patient computer or mobile device hardware/firmware/software element or its is any The computer that suitable combination etc. assembles can be performed component and execute.Other system and method for embodiment can be at least partly It is presented as and/or is implemented as being configured as receiving the machine of the computer-readable medium of storage computer-readable instruction.These Instruction can by equipment and collection of network with the above-mentioned type at computer component can be performed execute.Computer-readable medium energy It is stored in such as RAM, ROM, flash memory, EEPROM, optical device (CD or DVD), hard disk drive, floppy disk drive or any On any suitable computer-readable medium of suitable equipment.It can be processor that component, which can be performed, in computer, but any suitable Special hardware can (alternatively or additionally) execute instruction.
These figures illustrate according to preferred embodiment, example construction and its modification, composition, method and system can Structure, the function and operation of the realization of energy.It shall also be noted that in some alternative embodiments, the function of referring to can not be according to The sequence pointed out in figure occurs.For example, being based on related function, the aspect continuously shown actually can substantially simultaneously be held Capable or aspect can execute in reverse order sometimes.Embodiment includes the every of various system components and various method processes A combination and displacement, including any modification, embodiment and specific embodiment.As those skilled in the art will retouch in detail from previous It states and is recognized from drawings and claims, can modify and change without departing from range to embodiment.

Claims (22)

1. a kind of system for characterizing alimentary canal associated disease group, wherein the alimentary canal associated disease group is related with microorganism Taxonomical unit set associative, the system comprises:
● taxonomy database, the taxonomy database include being directed to and the associated grouping sheet of the alimentary canal associated disease group The reference relative abundance range set of position set；
● processing system, the processing system can be operated to collect the container for including biomaterial, the processing system from user System includes the sequenator system that can be operated to determine the microorganism sequence data set of the user from the biomaterial；
● group characterization system, described group of characterization system can operate with:
O determines user's relative abundance of the taxonomical unit set for the user based on the microorganism sequence data set Range；
O generate user's relative abundance range set with it is described with reference between relative abundance range set compared with；
O determines the group characterization of the alimentary canal associated disease group of the user based on the comparison；And
● treatment system, the treatment system can be operated to be promoted based on described group of characterization for the alimentary canal associated disease The treatment of the alimentary canal associated disease of group.
2. system described in claim 1, wherein the taxonomy database includes that the reference that is obtained by following item is relatively rich Spend range set:
● the determining target set with the associated taxonomical unit of alimentary canal associated disease group,
● determine reference mark object set；With
● it determines based on the reference mark object set selected point compared between the target set of the taxonomical unit The described of class unit set refers to relative abundance range set.
3. system as claimed in claim 2, wherein determine that the reference mark object set includes based on described in prediction reading determination Reference mark object set, the prediction reading is from based on the selected primer of marker feature shared across multiple grouping sheet hytes Group obtains.
4. system as claimed in claim 3, wherein between the reference mark object set and the target set of the taxonomical unit Comparison include sequence between the prediction reading and the reference microorganism sequence of the target set associative of the taxonomical unit Similitude.
5. system as claimed in claim 3, wherein the processing system can be operated based on the primer for using the primer sets The nucleic acid from the biomaterial is expanded to determine the microorganism sequence data set, wherein the primer targeting corresponds to With the microorganism sequence of the associated grouping sheet hyte of the alimentary canal associated disease, and wherein, the taxonomical unit set packet Include grouping sheet hyte.
6. system described in claim 1, wherein the treatment system can be operated to be conducive to consume based on described group of characterization The supply of product treatment, wherein consumables treatment can be operated with influencing the user with the alimentary canal associated disease At least one of associated microbial population composition and microbial population function, to promote the alimentary canal associated disease state Improvement.
7. system described in claim 1, wherein the taxonomical unit set includes at least one of following item: another branch bacterium Alistipes (category), Barnesiella (category), Bifidobacterium Bifidobacterium (category), campylobacter Campylobacter (category), Peptoclostridium (category), angstrom Xi Shi-bacillus dysenteriae Escherichia-Shigella (category), Fusobacterium Fusobacterium (category), lactobacillus Lactobacillus (category), Odoribacter (category), general Salmonella Prevotella (category), Pseudoflavonifractor (category), Ross Salmonella Roseburia (category), Ruminococcus Ruminococcus (category), salmonella Salmonella (category), Veillonella Veillonella (category), Ackermam Salmonella Akkermansia muciniphila (kind), Anaerotruncus colihominis (kind), bacteroides fragilis Bacteroides fragilis (kind), bacteroides vulgatus Bacteroides vulgatus (kind), bifidobacterium longum Bifidobacterium longum (kind), Butyrivibrio crossotus Butyrivibrio crossotus (kind), jejunum campylobacter bar Bacterium Campylobacter jejuni (kind), campylobacter coli Campylobacter coli (kind), Black-Headed Gull campylobacter Campylobacter lari (kind), Peptoclostridium difficile (kind), gas Collins bacterium Collinsella is produced Aerofaciens (kind), rule fecal bacteria Coprococcus eutactus (kind), Desulfovibrio piger (kind), Dialister invisus (kind), Escherichia coli Escherichia coli (kind), Escherichia coli O 157 Escherichia Coli O157 (kind), pula clostridium Faecalibacterium prausnitzii (kind), Smith's methagen Methanobrevibacter smithii (kind), Oxalobacter formigenes Oxalobacter formigenes (kind), white Ruminococcus Ruminococcus albus (kind), Ruminococcus bromii Ruminococcus bromii (kind), active cud ball Bacterium Ruminococcus gnavus (kind), Salmonella enteritidis Salmonella enterica (kind), Bang Geer salmonella Salmonella bongori (kind), Shigella boydii Shigella boydii (kind), Shigella sonnei Shigella sonnei (kind), shigella flexneri Shigella flexneri (kind), shigella dysenteriae Shigella Dysenteriae (kind), Streptococcus sanguis Streptococcus sanguinis (kind), streptococcus thermophilus Streptococcus Thermophilus (kind), comma bacillus Vibrio cholerae (kind) and yersinia enterocolitica Yersinia Enterocolitica (kind).
8. system as claimed in claim 7, wherein the taxonomical unit set further comprises at least one of following item: quasi- Prey irrigate bacterium Alloprevotella (category), anaerobism microbacterium (microbacteria) Anaerofilum (category), bacteroid Bacteroides (category), Blautia (category), butyric acid vibrios Butyricimonas (category), Catenibacterium (category), Christensenella (category), Collinsella (category), fecal bacteria Coprococcus (category), dialister bacterium Dialister (category), Iger hereby Salmonella It is Eggerthella (category), bacillus faecalis Faecalibacterium (category), Flavonifractor (category), Gelria (category), bloodthirsty Bacillus Haemophilus (category), Holdemania (category), the bacillus Oscillibacter (category) that quivers, quiver spirillum Oscillospira (category), Parabacteroides (category), Paraprevotella (category), koala bacillus Phascolarctobacterium (category), streptococcus Streptococcus (category), Turicibacter (category), Tyzzerella (category), Acetobacter Nitrogenifigens (kind), Acinetobacter bauamnnii Acinetobacter baumannii (kind), Azospirillum brasilense Azospirillum brasilense (kind), Bacillus cercus Bacillus cereus (kind), bacillus coagulans Bacillus coagulans (kind), bacillus licheniformis Bacillus licheniformis (kind), animal bifidobacteria Bifidobacterium animalis (kind), bifidobacterium bifidum Bifidobacterium bifidum (kind), side spore gemma Bacillus Brevibacillus laterosporus (kind), small Harald Christensen Salmonella Christensenella minuta The stick-like bacillus Clavibacter michiganensis (kind) in (kind), Michigan, clostridium butyricum Clostridium Butyricum (kind), italic enterococcus Enterococcus italicus (kind), succinic acid filiform bacillus Fibrobacter is produced Succinogenes (kind), thermophilic cock Salmonella Kocuria rhizophila (kind), Lactobacillus brevis Lactobacillus Brevis (kind), Lactobacillus coryniformis Lactobacillus coryniformis (kind), bacillus acidificans longissimus Lactobacillus delbrueckii (kind), lactobacillus fermenti Lactobacillus fermentum (kind), Switzerland's cream bar Bacterium Lactobacillus helveticus (kind), Kefir grains matrix lactobacillus Lactobacillus kefiranofaciens (kind), Lactobacillus kunkeei (kind), Lactobacillus rhamnosus Lactobacillus rhamnosus (kind), saliva cream Bacillus Lactobacillus salivarius (kind), Fiji galactococcus Lactococcus fujiensis (kind), grignard milk-globule Bacterium Lactococcus garvieae (kind), Lactococcus lactis Lactococcus lactis (kind), Leptotrichia Hofstadii (kind), Leuconostoc fallax (kind), pickles leukonid Leuconostoc kimchii (kind), drinks Wine coccus Oenococcus oeni (kind), bee are like bacillus Paenibacillus apiarius (kind), Pediococcus pentosaceus Pediococcus pentosaceus (kind), propionibacterium freudenreichii Propionibacterium freudenreichii (kind), The stick-like bacillus Pseudoclavibacter helvolus (kind) of greenish yellow vacation, salmon Renibacterium Renibacterium Salmoninarum (kind), ruminococcus flavefaciens Ruminococcus flavefaciens (kind), Staphylococcus sciuri Staphylococcus sciuri (kind), South Korea Wei Si Salmonella Weissella koreensis (kind), clostridium Clostridium (category) and clostridium difficile Clostridium difficile (kind).
9. system according to any one of claims 8, wherein it is described treatment include for the alimentary canal associated disease probiotics it is related Therapy, wherein the related therapy of the probiotics is related to the taxonomical unit set, and wherein, the treatment system includes For promote to from the relevant probiotics of the grouping sheet hyte of the taxonomical unit set in relation to the interface treated.
10. a kind of characterization is with the microorganism of taxonomical unit set associative in relation to the method for illness group, which comprises
● taxonomy database is generated, the taxonomy database includes the fixed reference feature with the taxonomical unit set associative；
● microorganism sequence data set is generated for user based on the biological sample collected from the user；
● being based on the microorganism sequence data set is user's extraction group correlated characteristic set；
● the fixed reference feature is determined for the user and organizes the comparison between correlated characteristic set；
● relatively determine that the microorganism characterizes in relation to group of the illness group to user according to described；With
● it is based on described group of characterization, promotes to be directed to treatment of microorganism of the microorganism in relation to illness group in relation to illness.
11. method described in any one of claim 10, wherein promoting the treatment includes being promoted based on described group of characterization to the user Probiotics consumables, wherein the probiotics consumables can be operated with a variety of institutes in relation to illness group that improve the microorganism State the related illness of microorganism.
12. method described in claim 11, the method further includes: it collects associated with the dietary behavior of the user The relevant supplementary data set of diet, wherein promoting the probiotics consumables includes based on the relevant supplementary data of the diet Collection and described group of characterization promote the probiotics consumables to user.
13. method described in any one of claim 10, wherein extracting described group of correlated characteristic set includes based on the microorganism sequence Data set extracts the microbial population Diversity Characteristics and microbial population functional diversity of described group of correlated characteristic set Feature, and wherein it is determined that the comparison include determine the fixed reference feature and the microbial population Diversity Characteristics and The comparison of the microbial population functional diversity feature.
14. method described in any one of claim 10, wherein the related illness group of the microorganism includes and the associated alimentary canal of antibiotic Associated disease set, wherein extracting described group of correlated characteristic set includes based on described in microorganism sequence data set extraction The microbial population pharmacogenomics feature of group correlated characteristic set, and wherein, promoting treatment includes being based on the microorganism Group is that pharmacogenomics feature promotes the antibiotic associated treatment for being directed to the alimentary canal associated disease set.
15. method described in any one of claim 10, wherein determine the ratio between the fixed reference feature and described group of correlated characteristic set Relatively include the associated described group of correlated characteristic set of at least one of determining and following item: microbial population composition characteristic is deposited , the shortage of microbial population composition characteristic, the relative abundance including taxology feature of the grouping sheet hyte of taxonomical unit set Between the diversity of microbial population composition and at least two features of the taxonomical unit set associative of functional character The systematic growth distance between interaction and the grouping sheet hyte between ratio, the grouping sheet hyte.
16. method of claim 15,
● wherein, the reference relative abundance range set that the taxonomy database includes the determining taxonomical unit set is generated, It is wherein, described to be associated with reference to relative abundance range set illness group related with the microorganism,
● wherein, extracting described group of correlated characteristic set includes extracting the taxonomical unit based on the microorganism sequence data set User's relative abundance range set of set, and
● wherein it is determined that the fixed reference feature includes determining the reference compared with described between described group of correlated characteristic set Relative abundance range set is compared with described between user's relative abundance range set.
17. method described in claim 16, wherein determine the reference relative abundance range set packet of the taxonomical unit set It includes:
● the set of supplement biological sample set and supplementary data set is collected for user group；
● the use associated primer sets of illness group related with the microorganism handle the supplement biological sample set and are mended with generating Fill microorganism sequence data set；With
● based on the supplement microorganism sequence data set and the supplementary data set set determine it is described with reference to relative abundance The set of range.
18. method of claim 15, wherein determine the ratio between the fixed reference feature and described group of correlated characteristic set It relatively include executing at least one of following item: forecast analysis, multihypothesis test, random forest inspections, principal component analysis, significantly Sex index analysis, risk score analysis and meta-analysis.
19. method described in any one of claim 10, wherein promoting the treatment includes promoting for the related illness of the microorganism The related treatment of probiotics, wherein the probiotics is related to be treated and the taxonomical unit set associative, and the wherein classification Unit set includes at least one in following item: bacillus coagulans Bacillus coagulans (kind), animal bifidobacteria Bifidobacterium animalis (kind), clostridium butyricum Clostridium butyricum (kind), Lactobacillus brevis Lactobacillus brevis (kind), Lactobacillus coryniformis Lactobacillus coryniformis (kind), lactobacillus fermenti Lactobacillus fermentum (kind), Lactobacillus helveticus Lactobacillus helveticus, Lactobacillus rhamnosus Lactobacillus rhamnosus (kind) and streptococcus salivarius Streptococcus salivarius (kind).
20. method described in claim 19, wherein the taxonomical unit set further comprises at least one in following item: Acetobacter nitrogenifigens (kind), Azospirillum brasilense Azospirillum brasilense (kind), lichens Bacillus licheniformis (kind), bifidobacterium bifidum Bifidobacterium bifidum (kind), side Spore bacillus Brevibacillus laterosporus (kind), the stick-like bacillus Clavibacter in Michigan Michiganensis (kind), italic enterococcus Enterococcus italicus (kind), thermophilic cock Salmonella Kocuria Rhizophila (kind), bacillus acidificans longissimus Lactobacillus delbrueckii (kind), Kefir grains matrix cream bar Bacterium Lactobacillus kefiranofaciens (kind), Lactobacillus kunkeei (kind), Lactobacillus salivarius Lactobacillus salivarius (kind), Lactococcus garvieae Lactococcus garvieae (kind), Lactococcus lactis Lactococcus lactis (kind), Leptotrichia hofstadii (kind), Leuconostoc fallax (kind), pickles Leukonid Leuconostoc kimchii (kind), Oneococcus onei Oenococcus oeni (kind), bee are like bacillus Paenibacillus apiarius (kind), Pediococcus pentosaceus Pediococcus pentosaceus (kind), propionibacterium freudenreichii Propionibacterium freudenreichii (kind), the stick-like bacillus Pseudoclavibacter helvolus of greenish yellow vacation (kind), salmon Renibacterium Renibacterium salmoninarum (kind), ruminococcus flavefaciens Ruminococcus Flavefaciens (kind), Staphylococcus sciuri Staphylococcus sciuri (kind), streptococcus dysgalactiae Streptococcus dysgalactiae (kind), Streptococcus parauberis (kind) and South Korea Wei Si Salmonella Weissella koreensis (kind).
21. method described in any one of claim 10, wherein the related illness group of the microorganism includes at least one of following item: Diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), Crohn disease, ulcerative colitis, constipation, abdominal tenderness, abdomen Swollen, ventosity, obesity, type-2 diabetes mellitus, prediabetes, kidney stone, cardiovascular health and anxiety.
22. method described in any one of claim 10, wherein characterizing the microorganism in relation to characterization group includes diagnosing and treating alimentary canal At least one of associated disease group.
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