Methods and systems for microbiome characterization, monitoring and treatment

• US 10,633,714 B2
• Filed: 07/21/2014
• Issued: 04/28/2020
• Est. Priority Date: 07/21/2013
• Status: Active Grant

• Current Assignee: Pendulum Therapeutics, Inc.
• Original Assignee: Pendulum Therapeutics, Inc.
• Inventors: Cutcliffe, Colleen, Eid, John S., Bullard, James H.
• Primary Examiner(s): Wise, Olivia M.
• Application Number:
  US14/437,133
• Publication Number:
  US 20150259728A1
• Time in Patent Office: 2,108 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/689 for bacteria
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present disclosure provides methods for profiling a microbiome and therapeutic compositions for treatment. Additionally, the methods, systems, compositions and kits provided herein are directed to assessing or predicting health status in a subject. Some of the embodiments include generating a report.

Claims

1. A method of profiling a microbiome by assaying a biological sample of a subject, the method comprising:

(a) obtaining said biological sample from said subject, wherein said biological sample comprises a plurality of microbes, wherein said subject has or is suspected of having type 2 diabetes;

(b) subjecting nucleic acid molecules extracted from said plurality of microbes to sequencing to obtain nucleic acid sequence reads that comprise ribosomal RNA operon sequences from said plurality of microbes, wherein at least one of said nucleic acid sequence reads provides a contiguous sequence spanning at least a 16S region of said ribosomal RNA operon, a 23 S region of said ribosomal RNA operon, or an intergenic region between said 16S region and said 23 S region of said ribosomal RNA operon;

(c) aligning said nucleic acid sequence reads of said ribosomal RNA operon sequences to one or more reference sequences to identify said plurality of microbes at a strain level;

(d) using a database to identify metabolic pathways that correspond said plurality of microbes identified at said strain level in (c); and

(e) based on (d), administering a microbial-based composition to said subject, thereby treating said type 2 diabetes.

2. The method of claim 1, wherein at least one of said nucleic acid sequence reads comprises said contiguous sequence spanning at least said 16S region.

3. The method of claim 1, wherein at least one of said nucleic acid sequence reads comprises said contiguous sequence spanning at least said 23S region.

4. The method of claim 1, wherein at least one of said nucleic acid sequence reads comprises said contiguous sequence spanning said intergenic region between said 16S region and said 23S region of said ribosomal RNA operon.

5. The method of claim 1, wherein said plurality of microbes in said microbiome profile comprises 800 or fewer microbes.

6. The method of claim 1, further comprising obtaining said nucleic acid molecules from said plurality of microbes in biological samples taken at least at two different points of time.

7. The method of claim 1, wherein a presence or absence of said plurality of microbes and said metabolic pathways is indicative of said subject having said type 2 diabetes.

8. The method of claim 1, further comprising detecting or measuring an amount of said nucleic acid sequence reads of said plurality of microbes.

9. The method of claim 8, wherein said detecting or measuring said amount of said nucleic acid sequence reads of said plurality of microbes comprises detecting levels of markers from said plurality of microbes.

10. The method of claim 1, wherein at least one of said nucleic acid sequence reads provides a contiguous sequence spanning said 16S region and said 23 S region of said ribosomal RNA operon.

11. The method of claim 1, wherein each of said nucleic acid sequence reads is longer than 2000 bases.

12. The method of claim 1, wherein said sequencing of (b) is performed using a long read sequencing platform.

13. The method of claim 1, further comprising extracting said nucleic acid molecules from said plurality of microbes in said biological sample.