Method and system for microbiome-derived characterization, diagnostics and therapeutics for cardiovascular disease conditions

Patent metadata

Field	Value
Publication number	US-9754080-B2
Application number	US-201615098081-A
Country	US
Kind code	B2
Filing date	Apr 13, 2016
Priority date	Oct 21, 2014
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

A method for at least one of characterizing, diagnosing, and treating a cardiovascular disease condition in at least 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 cardiovascular disease condition based upon 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 configured to correct the cardiovascular disease condition; 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 at least one of characterizing, diagnosing, and treating a cardiovascular disease condition in at least a subject, the method comprising:
for each of an aggregate set of samples from a population of subjects:
determining a microorganism nucleic acid sequence, comprising:
identifying primers for nucleic acid sequences associated with the cardiovascular disease condition,
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 cardiovascular disease condition;
generating a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects based on the alignment;
receiving a supplementary dataset, informative of characteristics associated with the cardiovascular disease condition, from the population of subjects;
transforming the supplementary dataset and features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset into a characterization model of the cardiovascular disease condition;
based upon the characterization model, generating a therapy model configured to improve a state of the cardiovascular disease condition; and
at an output device associated with the subject, providing a therapy to the subject with the cardiovascular disease condition based upon the characterization model and the therapy model, wherein the therapy modulates microbiome composition to improve a state of the cardiovascular disease condition.

2. The method of claim 1 , wherein processing content of each of the aggregate set of samples comprises performing a fragmentation operation, a multiplexed amplification operation using a set of primers, a sequencing operation, and an alignment operation with the aggregate set of samples.

3. 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 variations across a first subset of the population of subjects note exhibiting the cardiovascular disease condition and a second subset of the population of subjects exhibiting the cardiovascular disease condition.

4. The method of claim 2 , wherein generating the characterization model of the cardiovascular disease condition comprises generating a characterization that is diagnostic of at least one of coronary heart disease, inflammatory heart disease, and valvular heart disease.

5. The method of claim 4 , wherein generating the characterization that is diagnostic of coronary heart disease comprises generating the characterization upon processing the aggregate set of samples and determining presence of features derived from a set of taxa including: Varibaculum (genus), Actinomyces (genus), and Actinomycetaceae (family).

6. The method of claim 5 , further including generating the characterization upon determining presence of features derived from a set of functions associated with at least one of a Kyoto Encyclopedia of Genes and Genomes (KEGG) functional feature, a clusters of orthologous groups (COG) functional feature, and a Gene Ontology functional feature.

7. The method of claim 4 , wherein generating the characterization that is diagnostic of at least one of inflammatory heart disease and valvular heart disease comprises generating the characterization upon processing the aggregate set of samples and determining presence of features derived from at least one of: 1) a set of taxa and 2) a set of functions associated with at least one of a Kyoto Encyclopedia of Genes and Genomes (KEGG) functional feature and a clusters of orthologous groups (COG) functional feature.

8. The method of claim 2 , wherein generating the characterization model of the cardiovascular disease condition comprises generating a characterization that is diagnostic of a cardiovascular disease-associated condition including at least one of obesity and stroke.

9. The method of claim 8 , wherein generating the characterization that is diagnostic of obesity comprises generating the characterization upon processing the aggregate set of samples and determining presence of features derived from 1) a set of taxa including: Sarcina (genus), Bacteroides (genus), and Clostridiaceae (family), and 2) a set of functions associated with a first Kyoto Encyclopedia of Genes and Genomes (KEGG) functional feature related to cellular processes and signaling, a second KEGG functional feature related to ribosome biogenesis in eukaryotes, and a third KEGG functional feature related to Aminoacyl-tRNA biosynthesis.

10. The method of claim 8 , wherein generating the characterization that is diagnostic of stroke comprises generating the characterization upon processing the aggregate set of samples and determining presence of features derived from at least one of: 1) a set of taxa and 2) a set of functions associated with at least one of a Kyoto Encyclopedia of Genes and Genomes (KEGG) functional feature and a clusters of orthologous groups (COG) functional feature.

11. The method of claim 3 , 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 cardiovascular disease condition in association with a subset of the set of functional aspects, the subset derived from at least one of clusters of orthologous groups (COG) of proteins features, genomic functional features from the Kyoto Encyclopedia of Genes and Genomes (KEGG), genomic functional features from a Cluster of Orthologous Groups (COG) database, chemical functional features, and systemic functional features.

12. A method for characterizing a cardiovascular disease condition in a subject, the method comprising:
for each of an aggregate set of samples from a population of subjects:
determining a microorganism nucleic acid sequence, comprising:
identifying primers for nucleic acid sequences associated with the cardiovascular disease condition,
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 cardiovascular disease condition;

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 samples;
at the computing system, features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset into a characterization model of the cardiovascular disease condition, wherein the characterization model is diagnostic of at least one of coronary heart disease, inflammatory heart disease, and valvular heart disease;
based upon the characterization model, generating a therapy model configured to improve a state of the cardiovascular disease condition; and

at an output device associated with the subject, providing a therapy to the subject with the cardiovascular disease condition, upon processing a sample from the subject with the characterization model, in accordance with the therapy model, wherein

Assignees

• Ubiome Inc

Inventors

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

Classifications

• G06F19/28

  Physics · mapped topic

• G01N2800/044

  Hyperlipemia or hypolipemia, e.g. dyslipidaemia, obesity · CPC title

• G06F19/345

  Physics · mapped topic

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title

• G01N2800/32

  Cardiovascular disorders · CPC title