Granted Patent B2

US 10,380,325 · App. 15/606,975 · Granted Aug 13, 2019

Inventors: Zachary Apte (San Francisco, CA); Jessica Richman (San Francisco, CA); Daniel Almonacid (San Francisco, CA)

Assignee: uBiome, Inc.

G06F19/3418C12Q1/68C12Q1/689C12Q1/6883G06F19/00G06F19/10G06F19/12G06F19/28G06F19/30G16H20/10G16H50/20C12Q2600/118Y02A90/26

Abstract

Claims (60)

1. A method for diagnosing and treating a celiac condition for 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:

with an in silico operation applied to a primer set including degenerate primers, identifying a primer for a nucleic acid sequence associated with the celiac condition, the primer having an adaptor region;

fragmenting nucleic acid material based on the biological sample;

tagging fragmented nucleic acid material of the biological sample with a sequencing adaptor associated with the adaptor region of the primer; and

amplifying the fragmented nucleic acid material based on the identified primer; and

determining an alignment of the microorganism nucleic acid sequence to a reference nucleic acid sequence associated with the celiac condition;

generating a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects based upon the alignments;

collecting a supplementary dataset, associated with at least a subset of the population of subjects, wherein the supplementary dataset is informative of a characteristic associated with the celiac condition;

generating a characterization of the celiac condition based upon the supplementary dataset and 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 celiac condition; and

at an output device associated with the subject and configured to be at least one of worn and retained near the subject, providing the therapy to the subject with the celiac condition based upon the characterization and the therapy model, wherein the therapy comprises a consumable that modulates microbiome composition of the subject towards an equilibrium state.

2. The method of claim 1 , further comprising:

providing a set of sampling kits to the population of subjects, each sampling kit of the set of sampling kits comprising a sample container configured to receive the biological sample from a collection site,

wherein determining the microorganism nucleic acid sequence comprises determining the microorganism nucleic acid sequence with a bridge amplification substrate of a next generation sequencing platform of a sample processing system, and

wherein generating the microbiome composition dataset and the microbiome functional diversity dataset comprises generating the microbiome composition dataset and the microbiome functional diversity dataset at computing devices operable to communicate with the next generation sequencing platform.

3. The method of claim 2 , wherein determining the microorganism nucleic acid sequence comprises performing, at a library preparation subsystem of the sample processing system, multiplex amplification with the fragmented nucleic acid material based on the identified primer.

4. The method of claim 1 , wherein the identifying the primer comprises identifying the primer for the nucleic acid sequence associated with at least one of: gastrointestinal discomfort, gluten intolerance, fatigue, and a nutritional deficiency.

5. The method of claim 1 , wherein the supplementary dataset comprises biometric sensor data informative of the celiac condition and sampled at a biometric sensor associated with the subject, wherein generating the characterization comprises:

determining a set of microbiome feature vectors based on the biometric sensor data and the at least one of the microbiome composition dataset and the microbiome functional diversity dataset; and

generating the characterization based on the set of microbiome feature vectors.

6. The method of claim 1 , wherein providing the therapy comprises automatically initiating a signal that controls a treatment device to provide the therapy to the subject with the celiac condition based upon the characterization and the therapy model.

7. The method of claim 1 , wherein generating the characterization of the celiac condition comprises generating the characterization based on a set of microbiome composition features extracted from the microbiome composition dataset, wherein the set of microbiome composition features are associated with a set of taxa comprising at least one of: Clostridium (genus), Oscillibacter (genus), Sutterella (genus), Clostridiaceae (family), Peptostreptococcaceae (family), Peptococcaceae (family), Oscillospiraceae (family), and Proteobacteria (phylum).

8. The method of claim 7 , further comprising presenting, at an interface operable to improve display of celiac condition information, the microbiome composition of the subject relative to a subject group sharing a demographic characteristic associated with the celiac condition, wherein the microbiome composition comprises the set of taxa.

9. The method of claim 8 , further comprising presenting, at the interface, a change in the microbiome composition over time in relation to the therapy and the celiac condition.

10. The method of claim 7 , wherein the microbiome composition features are associated with the set of taxa further comprising at least one of: Aparasutterella (genus), Bacteroides uniformis (species), Parasutterella excrementihominis (species), Bacteroides fragilis (species), Acidobacteria (phylum), Actinobacillus (genus), Actinobacillus porcinus (species), Pasteurellaceae (family), and Pasteurellales (order).

11. The method of claim 7 , wherein generating the characterization of the celiac condition comprises generating the characterization based on the set of microbiome composition features and a set of microbiome functional diversity features extracted from the microbiome functional diversity dataset, wherein the set of microbiome functional diversity features comprise at least one of: a COG (W) code derived feature, a putative membrane protein KEGG derived feature, a nitric oxide reductase subunit B KEGG derived feature, a competence protein ComGA KEGG derived feature, a competence protein ComGC KEGG derived feature, a DNA replication protein KEGG derived feature, a separation ring formation regulator KEGG derived feature, a glyceraldehyde-3-phosphate dehydrogenase (NADP+) KEGG derived feature, a leader peptidase (prepilin peptidase)/N-methyltransferase, a pyruvate oxidase KEGG derived feature, a MFS transporter, SHS family, sialic acid transporter KEGG derived feature, a medium-chain acyl-[acyl-carrier-protein] hydrolase KEGG derived feature, an acyl-CoA hydrolase KEGG derived feature, a glucan 1,6-alpha-glucosidase KEGG derived feature, a putative membrane protein KEGG derived feature, a hydroxymethylglutaryl-CoA reductase KEGG derived feature, a penicillin-binding protein KEGG derived feature, a competence protein CoiA KEGG derived feature, an aminotransferase KEGG derived feature, an X-pro dipeptidyl-peptidase KEGG derived feature, a SprT-like protein KEGG derived feature, a general stress protein 13 KEGG derived feature, a competence protein ComGF KEGG derived feature, a penicillin-binding protein 2A KEGG derived feature, a para-aminobenzoate synthetase/4-amino-4-deoxychorismate lyase KEGG derived feature, an uncharacterized protein KEGG derived feature, a competence protein ComFA KEGG derived feature, and a GMP reductase KEGG derived feature.

12. A method for characterizing a celiac condition for a subject, the method comprising:

for a biological sample associated with a population:

determining a microorganism nucleic acid sequence, comprising:

with an in silico operation applied to a primer set including degenerate primers, identifying a primer for a nucleic acid sequence associated with the celiac condition, the primer having an adaptor region;

fragmenting nucleic acid material based on the biological sample;

tagging fragmented nucleic acid material of the biological sample with a sequencing adaptor associated with the adaptor region of the primer; and

amplifying the fragmented nucleic acid material based on the identified primer; and

determining an alignment of the microorganism nucleic acid sequence to a reference nucleic acid sequence associated with the celiac condition;

generating at least one of a microbiome composition dataset and a microbiome functional diversity dataset based on the alignment;

receiving a supplementary dataset associated with the celiac condition and at least a subset of the population;

generating a characterization of the celiac condition based upon the supplementary dataset and the at least one of the microbiome composition dataset and the microbiome functional diversity dataset;

based upon the characterization, generating a therapy model operable to determine a therapy; and

at an output device associated with the subject and configured to be at least one of worn and retained near the subject, providing the therapy to the subject based upon the therapy model, wherein the therapy comprises a consumable that is operable to modulate microbiome composition of the subject in association with the celiac condition.

13. The method of claim 12 , further comprising:

generating a characterization model for the celiac condition based on the characterization; and

diagnosing the subject with the celiac condition based on the characterization model and at least one of a subject microbiome composition dataset and a subject microbiome functional diversity dataset associated with a subject biological sample from the subject.

14. The method of claim 13 , wherein diagnosing the subject with the celiac condition comprises determining a celiac condition risk for the subject based on the characterization model and the at least one of the subject microbiome composition dataset and the subject microbiome functional diversity dataset, wherein the therapy is operable to reduce the celiac condition risk.

15. The method of claim 12 ,

wherein generating the characterization of the celiac condition comprises generating the characterization based on a set of microbiome composition features extracted from the microbiome composition dataset and on a set of microbiome functional diversity features extracted from the microbiome functional diversity dataset,

wherein the set of microbiome composition features are associated with a set of taxa comprising at least one of: Clostridium (genus), Oscillibacter (genus), and Sutterella (genus), and

wherein the set of microbiome functional diversity features comprise at least one of: a COG (W) code derived feature, a putative membrane protein KEGG derived feature, and a nitric oxide reductase subunit B KEGG derived feature.

16. The method of claim 15 ,

wherein the microbiome composition features are associated with the set of taxa further comprising at least one of: Aparasutterella (genus), Bacteroides uniformis (species), Parasutterella excrementihominis (species), Bacteroides fragilis (species), Actinobacillus (genus), and Actinobacillus porcinus (species), and

wherein the set of microbiome functional diversity features further comprise at least one of: a competence protein ComGA KEGG derived feature, a competence protein ComGC KEGG derived feature, a DNA replication protein KEGG derived feature, a separation ring formation regulator KEGG derived feature, a glyceraldehyde-3-phosphate dehydrogenase (NADP+) KEGG derived feature, a leader peptidase (prepilin peptidase)/N-methyltransferase, a pyruvate oxidase KEGG derived feature, a MFS transporter, SHS family, sialic acid transporter KEGG derived feature, a medium-chain acyl-[acyl-carrier-protein] hydrolase KEGG derived feature, an acyl-CoA hydrolase KEGG derived feature, a glucan 1,6-alpha-glucosidase KEGG derived feature, a putative membrane protein KEGG derived feature, a hydroxymethylglutaryl-CoA reductase KEGG derived feature, a penicillin-binding protein KEGG derived feature, a competence protein CoiA KEGG derived feature, an aminotransferase KEGG derived feature, an X-pro dipeptidyl-peptidase KEGG derived feature, a SprT-like protein KEGG derived feature, a general stress protein 13 KEGG derived feature, a competence protein ComGF KEGG derived feature, a penicillin-binding protein 2A KEGG derived feature, a para-aminobenzoate synthetase/4-amino-4-deoxychorismate lyase KEGG derived feature, an uncharacterized protein KEGG derived feature, a competence protein ComFA KEGG derived feature, and a GMP reductase KEGG derived feature.

17. The method of claim 16 , wherein providing the therapy comprises providing at least one of a probiotic therapy and a prebiotic therapy to the subject, wherein the at least one of the probiotic therapy and the prebiotic therapy is operable to selectively modulate a population size of a desired taxon associated with at least one of the set of microbiome composition features and at least one of the microbiome functional diversity features.

18. The method of claim 15 , wherein generating the characterization comprises generating the set of microbiome composition features based on a statistical analysis for the set of taxa, wherein the statistical analysis is associated with at least one of: relative abundance, differential relative abundance, presence, and absence.

19. The method of claim 18 , wherein the statistical analysis comprises at least one of a Kolmogorov-Smirnov test and a t-test.

20. The method of claim 12 , further comprising:

after providing the therapy, receiving a post-therapy biological sample from the subject;

processing the post-therapy biological sample based on the identified primer;

generating a post-therapy characterization of the subject in relation to the celiac condition and the therapy based on the processed post-therapy biological sample; and providing an updated therapy to the subject with the celiac condition based on the therapy model and the post-therapy characterization.

Assignments (3)

Continuity (12)