# US 10,246,753 B2 · Method and system for characterizing mouth-associated conditions

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- Number: US 10,246,753 B2
- Document ID: US10246753B2
- Status: Granted
- Kind: B2
- Application number: 15/452,529
- Filed: 2017-03-07
- Published: 2017-06-22
- Granted: 2019-04-02
- Earliest claimed: 2015-04-13
- Assignees: uBiome, Inc.
- Applicants: uBiome, Inc.
- Inventors: Zachary Apte; Catalina Valdivia; Daniel Almonacid; Jessica Richman
- Web page: https://patentgrep.com/patent/US10246753B2

## CPC

- G16H 40/67: for remote operation
- C12Q 1/689: for bacteria
- G01N 33/48792: {Data management, e.g. communication with processing unit (for in vivo diagnostics A61B5/0002; transmission systems for measured values G08C)}
- G16B 35/00: ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
- G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B 50/00: ICT programming tools or database systems specially adapted for bioinformatics
- G16B 50/10: Ontologies; Annotations
- G16B 50/20: Heterogeneous data integration
- G16B 50/30: Data warehousing; Computing architectures
- G16C 20/60: In silico combinatorial chemistry
- G16H 20/40: relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/16: Primer sets for multiplex assays
- G16H 10/40: for data related to laboratory analysis, e.g. patient specimen analysis
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H 20/60: relating to nutrition control, e.g. diets
- G16H 40/63: for local operation
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G16H 50/30: for calculating health indices; for individual health risk assessment
- G16H 50/50: for simulation or modelling of medical disorders
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Embodiments of a system and method for characterizing a mouth-associated condition in relation to a user can include one or more of: a handling network operable to collect containers including material from a set of users, the handling network including a sequencing system operable to determine microorganism sequences from sequencing the material; a microbiome characterization system operable to determine microbiome composition data and microbiome functional diversity data based on the microorganism sequences, collect supplementary data associated with the mouth-associated condition for the set of users, and transform the supplementary data and features extracted from the microbiome composition data and the microbiome functional diversity data into a characterization model for the mouth-associated condition; and/or a therapy system operable to promote a treatment to the user based on characterizing the user with the characterization model in relation to the mouth-associated condition.

## Claims

### Claim 1

A system for evaluating a mouth-associated condition in relation to a user, the system comprising:
a handling network operable to collect containers comprising material from a set of users, the handling network comprising:
a library preparation system operable to fragment and perform multiplex amplification on the material using a primer compatible with a genetic target associated with the mouth-associated condition;
a sequencing system operable to determine microorganism sequences from sequencing the material;
a microbiome characterization system operable to:
determine microbiome composition data and microbiome functional diversity data based on an alignment between the microorganism sequences and reference sequences associated with the mouth-associated condition,
collect supplementary data associated with the mouth-associated condition for the set of users, and
transform the supplementary data and features extracted from the microbiome composition data and the microbiome functional diversity data into a characterization model for the mouth-associated condition; and
a treatment system operable to provide a treatment to the user based on characterizing the user with the characterization model in relation to the mouth-associated condition.

### Claim 2 (depends on 1)

The system of claim 1, wherein the microbiome characterization system is further operable to:
extract microbiome composition features from the microbiome composition data based on a first mouth-associated feature-selection rule; and
extract microbiome functional diversity features from the microbiome functional diversity data based on a second mouth-associated feature-selection rule, wherein the features comprise the microbiome composition features and the microbiome functional diversity features.

### Claim 3 (depends on 2)

The system of claim 2, wherein the first and the second mouth-associated feature-selection rules improve the microbiome characterization system by facilitating decreased processing time to transform the supplementary data and the features into the characterization model.

### Claim 4 (depends on 2)

The system of claim 2, wherein the microbiome functional diversity features comprises at least one of: a cluster of orthologous group of proteins feature, a genomic functional feature, a taxonomic feature, a chemical functional feature, and a systemic functional feature.

### Claim 5 (depends on 1)

The system of claim 1, wherein the features comprise Kyoto Encyclopedia of Genes and Genomes (KEGG) functional features associated with at least one of: sulfur relay system, restriction enzyme, energy metabolism, immune system disease, fatty acid biosynthesis, carbon fixation pathways in prokaryotes, selenocompound metabolism, protein kinases, energy metabolism, glycerophospholipid metabolism, inorganic ion transport and metabolism, amino acid related enzymes, and carbon fixation in photosynthetic organisms.

### Claim 6 (depends on 5)

The system of claim 5, wherein the features associated with microbiome composition, comprise features derived from at least one of: relative abundance monotonic transformations and non-monotonic transformations.

### Claim 7 (depends on 6)

The system of claim 6, wherein transformation of features associated with microbiome composition comprise at least one of: normalizations, features vectors derived from latent variables analyses being linear or not-linear alternatives, linear or non-linear regression, kernel methods, features embedding methods, machine learning and/or statistical inference methods.

### Claim 8 (depends on 5)

The system of claim 5, wherein the features comprise a microbiome composition feature associated with a relative abundance of at least of: Neisseria elongata and Bergeyella sp. AF14.

### Claim 9 (depends on 1)

The system of claim 1, further comprising an interface operable to improve display of mouth-associated condition information derived from the characterization model, wherein the mouth-associated condition information comprises a microbiome composition for the user relative to a user group sharing a demographic characteristic, and wherein the microbiome composition comprises taxonomic groups comprising at least one of: Spirochaetes, Firmicutes, Proteobacteria, Actinobacteria, Fusobacteria, Bacteroidetes, TM7, Chloroflexi, Tenericutes, Elusimicrobia, Synergistetes, Porphyromonas gingivalis, Tannerella forsythia, Treponema detnicola, Streptococcus, Rothia, Actinomyces, Haemophilus, Lautropia, Leptotrichia, Prevotella, Porphyromonas, Selenomonas, Peptococcus, Catonella, Eubacterium, Oribacterium (Genus), Bacteroidia (Class), Flavobacteriia (Class), Erysipelotrichia (Class), Epsilonproteobacteria (Class), Clostridia (Class), Coriobacteriaceae (Family), Flavobacteriaceae (Family), Porphyromonadaceae (Family), Erysipelotrichaceae (Family), Peptostreptococcaceae (Family), Lachnospiraceae (Family), Campylobacteraceae (Family), Fusobacteriaceae (Family), Streptococcaceae (Family), Alloprevotella (Genus), Capnocytophaga (Genus), Porphyromonas (Genus), Stomatobaculum (Genus), Kingella (Genus), Campylobacter (Genus), Aggregatibacter (Genus), Bergeyella (Genus), Lachnoanaerobaculum (Genus), Fusobacterium (Genus), Peptostreptococcus (Genus), Coriobacteriales (Order), Bacteroidales (Order), Flavobacteriales (Order), Erysipelotrichales (Order), Campylobacterales (Order), Clostridiales (Order), Lactobacillales (Order), Bacteroidetes (Phylum), Candidatus Saccharibacteria (Phylum), Neisseria elongata (Species), Bergeyella sp. AF14 (Species), Capnocytophaga sputigena (Species), Peptostreptococcus stomatis (Species), Kingella oralis (Species), Prevotella nigrescens (Species), Porphyromonas catoniae (Species), Negativicutes (Class), Clostridiales Family XI, and Incertae Sedis (Family).

### Claim 10 (depends on 9)

The system of claim 9, wherein the mouth-associated condition information comprises a risk of infection for the user for at least one of: a gingivitis-associated condition and a halitosis-associated condition, and wherein the treatment is operable to reduce the risk of infection.

### Claim 11

A method for characterizing a mouth-associated condition in relation to a first user, the method comprising:
generating a microbiome composition dataset and a microbiome functional diversity dataset based on microorganism sequences derived from biological samples from a set of users, wherein generating the microbiome composition dataset and the microbiome functional diversity dataset comprises:
identifying primers for nucleic acid sequences associated with the mouth-associated condition,
fragmenting nucleic acid material,
amplifying the fragmented nucleic acid material using the identified primers, and
determining an alignment of the microorganism sequences to reference sequences associated with the mouth-associated condition;
receiving a supplementary dataset informative of the mouth-associated condition for the set of users;
obtaining a set of mouth-associated feature-selection rules correlating the mouth-associated condition to a subset of microbiome composition features and a subset of microbiome functional diversity features;
generating a feature set based on evaluating the microbiome composition dataset and the microbiome functional diversity dataset against the set of mouth-associated feature-selection rules;
applying the feature set with the supplementary dataset to generate a characterization model for the mouth-associated condition;
generating a first characterization of the first user in relation to the mouth-associated condition using the characterization model; and
providing a therapy to the first user based on the first characterization.

### Claim 12 (depends on 11)

The method of claim 11, wherein the characterization model is a gingivitis-associated characterization model, the method further comprising:
generating a second feature set based on the microbiome composition dataset and the microbiome functional diversity dataset;
applying the second feature set to generate a halitosis-associated characterization model; and
generating a second characterization of the first user in relation to a halitosis-associated condition using the halitosis-associated characterization model.

### Claim 13 (depends on 12)

The method of claim 12, wherein promoting the therapy to the first user is further based on the second characterization.

### Claim 14 (depends on 12)

The method of claim 12, wherein generating the second feature set comprises:
obtaining a set of halitosis-associated feature-selection rules correlating the halitosis-associated condition to a second subset of microbiome composition features and a second subset of microbiome functional diversity features; and
generating the second feature set based on evaluating the microbiome composition dataset and the microbiome functional diversity dataset against the set of halitosis-associated feature-selection rules.

### Claim 15 (depends on 11)

The method of claim 11, further comprising:
receiving a post-therapy biological sample from the first user;
generating a post-therapy characterization of the first user in relation to the mouth-associated condition based on the characterization model and the post-therapy biological sample; and
characterizing modulation of the mouth-associated condition in relation to the first user based on a comparison between the post-therapy characterization and the characterization.

### Claim 16 (depends on 15)

The method of claim 15, wherein the therapy is selected based on a therapy model, the method further comprising:
updating the therapy model based on the modulation of the mouth-associated condition in relation to the first user;
in response to updating the therapy model, updating a second therapy for a second user based on the updated therapy model; and
promoting the updated second therapy to the second user.

### Claim 17 (depends on 11)

The method of claim 11, wherein the supplementary dataset comprises biometric sensor data informative of the mouth-associated condition, wherein generating the feature set comprises generating a set of microbiome feature vectors based on the subset of microbiome composition features, the subset of microbiome functional diversity features, and a biometric feature derived from the biometric sensor data, and wherein applying the feature set comprises training the characterization model with the set of microbiome feature vectors.

### Claim 18 (depends on 17)

The method of claim 17, wherein the biometric sensor data comprises image data associated with the mouth-associated condition for the set of users, and wherein the biometric feature is derived from the image data.

### Claim 19 (depends on 11)

The method of claim 11, wherein the characterization comprises at least one of a gingivitis risk and a halitosis risk, and wherein the therapy is operable to facilitate modification of a microbiome composition and a microbiome functional diversity of the first user to reduce the at least one of the gingivitis risk and the halitosis risk.

### Claim 20 (depends on 19)

The method of claim 19, wherein generating the first characterization is based on inputting user microbiome composition features and user microbiome functional diversity features into the characterization model, the method further comprising:
receiving user supplementary data informative of the mouth-associated condition in relation to the first user;
determining a cause for the at least one of the gingivitis risk and the halitosis risk based on the user supplementary data, the user microbiome composition features, and the user microbiome functional diversity features; and
determining the therapy based on the cause.

### Claim 21 (depends on 20)

The method of claim 20, further comprising:
updating the characterization model based on the user supplementary data, the user microbiome composition features, and the user microbiome functional diversity features; and
in response to updating the characterization model, updating a second characterization for a second user based on the updated characterization model.

### Claim 22 (depends on 11)

The method of claim 11, wherein the mouth-associated condition comprises a gingivitis-associated condition, and wherein the subset of microbiome composition features comprises a composition feature associated with a set of taxa comprising at least one of: Spirochaetes, Firmicutes, Proteobacteria, Actinobacteria, Fusobacteria, Bacteroidetes, TM7, Chloroflexi, Tenericutes, Elusimicrobia, Synergistetes, Porphyromonas gingivalis, Tannerella forsythia, Treponema detnicola, Streptococcus, Rothia, Actinomyces, Haemophilus, Lautropia, Leptotrichia, Prevotella, Porphyromonas, Selenomonas, Peptococcus, Catonella, and Eubacterium.

### Claim 23 (depends on 22)

The method of claim 22, wherein the subset of microbiome functional diversity features comprises a Kyoto Encyclopedia of Genes and Genomes (KEGG) functional features associated with at least one of: sulfur relay system and restriction enzyme.

### Claim 24 (depends on 11)

The method of claim 11, wherein the mouth-associated condition comprises a halitosis-associated condition, and wherein the subset of microbiome composition features comprises a composition feature associated with a set of taxa comprising at least one of: Oribacterium (Genus), Bacteroidia (Class), Flavobacteriia (Class), Erysipelotrichia (Class), Epsilonproteobacteria (Class), Clostridia (Class), Coriobacteriaceae (Family), Flavobacteriaceae (Family), Porphyromonadaceae (Family), Erysipelotrichaceae (Family), Peptostreptococcaceae (Family), Lachnospiraceae (Family), Campylobacteraceae (Family), Fusobacteriaceae (Family), Streptococcaceae (Family), Alloprevotella (Genus), Capnocytophaga (Genus), Porphyromonas (Genus), Stomatobaculum (Genus), Kingella (Genus), Campylobacter (Genus), Aggregatibacter (Genus), Bergeyella (Genus), Lachnoanaerobaculum (Genus), Fusobacterium (Genus), Peptostreptococcus (Genus), Coriobacteriales (Order), Bacteroidales (Order), Flavobacteriales (Order), Erysipelotrichales (Order), Campylobacterales (Order), Clostridiales (Order), Lactobacillales (Order), Bacteroidetes (Phylum), Candidatus Saccharibacteria (Phylum), Neisseria elongata (Species), Bergeyella sp. AF14 (Species), Capnocytophaga sputigena (Species), Peptostreptococcus stomatis (Species), Kingella oralis (Species), Prevotella nigrescens (Species), Porphyromonas catoniae (Species), Negativicutes (Class), Clostridiales Family XI, and Incertae Sedis (Family).

### Claim 25 (depends on 24)

The method of claim 24, wherein the subset of microbiome functional diversity features comprises a Kyoto Encyclopedia of Genes and Genomes (KEGG) functional features associated with at least one of: Energy Metabolism, Immune System Diseases, Fatty acid biosynthesis, Carbon fixation pathways in prokaryotes, Selenocompound metabolism, Protein kinases, Energy metabolism, Glycerophospholipid metabolism, Inorganic ion transport and metabolism, Amino acid related enzymes, Carbon fixation in photosynthetic organisms, sulfur relay system, and restriction enzyme.

### Claim 26 (depends on 22)

The method of claim 22, wherein the composition feature is associated at least one of: Neisseria elongata (Species), Bergeyella sp. AF14 (Species), Capnocytophaga sputigena (Species), Peptostreptococcus stomatis (Species), Kingella oralis (Species), Prevotella nigrescens (Species), Porphyromonas catoniae (Species), Oribacterium (Genus), Alloprevotella (Genus), Capnocytophaga (Genus), Porphyromonas (Genus), Stomatobaculum (Genus), Kingella (Genus), Campylobacter (Genus), Aggregatibacter (Genus), Bergeyella (Genus), Lachnoanaerobaculum (Genus), Fusobacterium (Genus), Peptostreptococcus (Genus).

### Claim 27 (depends on 26)

The method of claim 26, wherein the composition feature of a single microorganism is associated with at least one of the following metrics: relative abundance, differential relative abundance, presence, and absence.