Method and system for microbiome-derived diagnostics and therapeutics

Patent metadata

Field	Value
Publication number	US-9703929-B2
Application number	US-201514919614-A
Country	US
Kind code	B2
Filing date	Oct 21, 2015
Priority date	Oct 21, 2014
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

A method for diagnosing and treating an immune microbial dysfunction in a subject, the method comprising: receiving an aggregate set of biological samples from a population of subjects; generating at least one of a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects; generating a characterization of the immune microbial dysfunction based upon features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset, wherein the characterization is diagnostic of at least one of Crohn's disease, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), ulcerative colitis, and celiac disease; based upon the characterization, generating a therapy model configured to correct the immune microbial dysfunction; and at an output device associated with the subject, promoting a therapy to the subject based upon the characterization and the therapy model.

First claim

We claim:

1. A method for diagnosing and treating an immune microbial dysfunction in a subject, the method comprising:
receiving an aggregate set of biological samples from a population of subjects;
for each biological sample of the aggregate set of biological samples:
determining a microorganism nucleic acid sequence, comprising:
identifying primers for nucleic acid sequences associated with the immune microbial dysfunction;
fragmenting nucleic acid material from the biological sample; and
amplifying the fragmented nucleic acid material using the identified primers; and

determining an alignment of the microorganism nucleic acid sequence to a reference nucleic acid sequence associated with the immune microbial dysfunction;

generating a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects based upon the alignment;
receiving a supplementary dataset, associated with at least a subset of the population of subjects, wherein the supplementary dataset is informative of characteristics associated with the immune microbial dysfunction;
generating a characterization of the immune microbial dysfunction based upon the supplementary dataset and features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset;
based upon the characterization, generating a therapy model that determines a therapy for correcting the immune microbial dysfunction; and
at an output device associated with the subject, providing a therapy to the subject with the immune microbial dysfunction based upon the characterization and the therapy model, wherein the therapy modulates microbiome composition of the subject towards an equilibrium state.

2. The method of claim 1 , wherein generating the characterization comprises performing a statistical analysis to assess a set of microbiome composition features and microbiome functional features having varying degrees of abundance in a first subset of the population of subjects exhibiting the immune microbial dysfunction and a second subset of the population of subjects not exhibiting the immune microbial dysfunction.

3. The method of claim 2 , wherein generating the characterization comprises:
extracting candidate features associated with a set of functional aspects of microbiome components indicated in the microbiome composition dataset to generate the microbiome functional diversity dataset; and
characterizing the immune microbial dysfunction in association with a subset of the set of functional aspects, the subset derived from at least one of clusters of orthologous groups of proteins features, genomic functional features from the Kyoto Encyclopedia of Genes and Genomes (KEGG), chemical functional features, and systemic functional features.

4. The method of claim 2 , wherein generating the characterization of the immune microbial dysfunction comprises generating a characterization that is diagnostic of at least one of Crohn's disease, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), ulcerative colitis, and celiac disease.

5. The method of claim 4 , wherein generating the characterization that is diagnostic of Crohn's disease comprises generating the characterization based on presence of features determined upon processing of the aggregate set of biological samples and derived from 1) a set of taxa including: Clostridium (genus), Flavonifractor (genus), Prevotella (genus), Clostridiaceae (family), Prevotellaceae (family), Oscillospiraceae (family), Gammaproteobacteria (class), and Proteobacteria (phylum) and 2) a set of functions associated with: a clusters of orthologous groups (COG) D code, a COG I code, and a COG J code.

6. The method of claim 4 , wherein generating the characterization that is diagnostic of IBS comprises generating the characterization based on presence of features determined upon processing of the aggregate set of biological samples and derived from a set of taxa including: Flavonifractor (genus), Odoribacter (genus), Blautia (genus), and Finegoldia (genus).

7. The method of Claim 4 , wherein generating the characterization that is diagnostic of IBD comprises generating the characterization based on presence of features determined upon processing of the aggregate set of biological samples and derived from 1) a set of taxa including: Clostridium (genus), Ruminococcus (genus), Clostridiaceae (family), Veillonellaceae (family), Selenomonadales (order), Gammaproteobacteria (class), Negativicutes (class), and Proteobacteria (phylum) and 2) a set of functions associated with at least one of a Kyoto Encyclopedia of Genes and Genomes (KEGG) K13015 code, a KEGG K07094 code, a KEGG K00318 code, and a KEGG K07482 code.

8. The method of claim 4 , wherein generating the characterization that is diagnostic of Ulcerative Colitis comprises generating the characterization based on presence of features determined upon processing of the aggregate set of biological samples and derived from a set of taxa including: Clostridium (genus), Lachnospira (genus), Blautia (genus), Dialister (genus), Ruminococcus (genus), Clostridiaceae (family), Peptostreptococcaceae (family), Veillonellaceae (family), Erysipelotrichaceae (family), Christensenellaceae (family), Erysipelotrichales (order), Gammaproteobacteria (class), and Erysipelotrichia (class).

9. The method of claim 4 , wherein generating the characterization that is diagnostic of Celiac Disease comprises generating the characterization based on presence of features determined upon processing of the aggregate set of biological samples and derived from a set of taxa including: Clostridium (genus), Oscillibacter (genus), Sutterella (genus), Clostridiaceae (family), Peptostreptococcaceae (family), Peptococcaceae (family), Oscillospiraceae (family), and Proteobacteria (phylum).

10. A method for diagnosing and treating an immune microbial dysfunction in a subject, the method comprising:
for each biological sample of an aggregate set of biological samples associated with a population of subjects:
determining a microorganism nucleic acid sequence, comprising:
identifying primers for nucleic acid sequences associated with the immune microbial dysfunction;
fragmenting nucleic acid material from the biological sample; and
amplifying the fragmented nucleic acid material using the identified primers; and

determining an alignment of the microorganism nucleic acid sequence to a reference nucleic acid sequence associated with the immune microbial dysfunction;

generating at least one of a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects based on the alignment, the microbiome functional diversity dataset indicative of systemic functions present in the microbiome components of the aggregate set of biological samples;
generating a characterization of the immune microbial dysfunction based upon features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset, wherein the characterization is diagnostic of at least one of Crohn's disease, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), ulcerative colitis, and celiac disease;
based upon the characterization, generating a therapy model that determine a therapy for correcting the immune microbial dysfunction; and
at an output device associated with the subject, providing a therapy to the subject based upon the characterization and the therapy model, wherein the therapy modulates microbiome composition of the subject towards an equilibrium state.

11. The method of claim 10 , wherein generating the characteriz

Assignees

• Apte Zachary
• Richman Jessica
• Behbahani Siavosh Rezvan
• Almonacid Daniel
• Ubiome Inc

Inventors

• Apte Zachary
• Richman Jessica
• Behbahani Siavosh Rezvan
• Almonacid Daniel

Classifications

• G16H10/40

  for data related to laboratory analysis, e.g. patient specimen analysis · CPC title

• G16H20/10

  relating to drugs or medications, e.g. for ensuring correct administration to patients · CPC title

• G16B99/00

  Subject matter not provided for in other groups of this subclass · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q1/689

  for bacteria · CPC title