This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice.

This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.

Background and Objectives:

There are few interventions or treatments to postpone or slow the progression of brain disease underlying cognitive disorders in old age. There is emerging evidence that clues to prevention maybe found in the gut microbiome, which communicates directly with brain via the vagus nerve or indirectly via the blood [1]. The gut microbiome can be manipulated by environmental factors, raising the possibility that effective intervention of environmental factors or behavior may be developed to reduce the burden of dementing disorders.
1. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 2012; 10(11): 735-42.

The microbiome is emerging as a fruitful new area of research into the mechanisms and pathology underlying chronic diseases. For instance links have been drawn between the microbiome characteristics (i.e., richness and compositional variety of, and tax counts inf the gut microbiome) and Type2 diabetes, obesity [2], and depression [3] and amyloid plaques [4] In our own research based on the Coronary Artery Risk Development in Young Adults (CARDIA) sub-study of the microbiome, we found microbiome richness, diversity and specific taxa are associated with hypertension (5) and cognitive function measured by a test of psychomotor speed (in preparation). While these data are suggestive of a gut-brain-vascular axis they provide no information on mechanisms, for instance, what metabolites are affected by the microbiome?; what are the genetic or environmental sources of these metabolites?; and do any of the metabolites lead us to possible candidate interventions to slow the progression of cerebro-vascular disease. Shotgun sequencing is a relatively new technology that can be used to profile taxonomic composition and functional potential of microbial communities and to recover whole genome sequences.

The overall program objectives are: 1) to identify a microbiome signature related
to cognitive function and brain MRI; 2) to identify pathways linking microbiota to
metabolic and genomic markers; 3) to identify interventions for early intervention
on cognitive impairment based on the pathways identified above.
2. Stols-Goncalves D, Tristao LS, Henneman P, Nieuwdorp M. Epigenetic Markers and
Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity,
Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease. Curr Diab
Rep 2019; 19(6): 31.
3. Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human
gut microbiota in quality of life and depression. Nat Microbiol 2019; 4(4): 623-32.
4. Moir RD, Lathe R, Tanzi RE. The antimicrobial protection hypothesis of Alzheimer's
disease. Alzheimers Dement 2018; 14(12): 1602-14.
5. Quince C, Walker AW, Simpson JT, Loman NJ, Segata N. Shotgun metagenomics,
from sampling to analysis. Nat Biotechnol 2017; 35(9): 833-44.
6. Sun S, Lulla A, Sioda M, et al. Gut Microbiota Composition and Blood Pressure. Hypertension 2019; 73(5): 998-1006.

Project Requirements:

The project should provide a comprehensive approach to microbiome research that includes basic sequencing using state-of-the-art techniques (i.e., whole metagenomic sequencing (WMS); post-processing algorithms to quality control, develop taxonomic profiles, and annotate the data with relevant metabolic pathways. Expertise is needed to compute standard measures of microbiome profiles, such as taxonomic trees, and measures of alpha and beta diversity, and to model relationships of microbiome taxonomic characteristics to clinical and sub-clinical disease outcomes. If warranted, more detailed analyses may be requested that link metabolomic, genetic and microbiome data together.

Specifically - Data processing includes: 1) Quality Control (QC) of raw Whole-Metagenome-Sequencing [WMS] data, 2) assignment of microbial features, including taxa, gene families, and metabolomics pathways using a range of packages (e.g., MetaPhlan, Kraken) and reference databases (e.g., KEGG, Enzyme Commission (EC), MinPath), 3) transformations and exclusions, as needed, to reduce sources of bias, and 4) derivation of within- (alpha-diversity) and between- (beta) person diversity measures (e.g., richness, Shannon Index, PCoA), individual taxonomic tree counts, and other standard figures, plots and microbiome descriptors.

Based on the tables generated from the WMS, the statistical analysis may include, with respect to study outcomes: 1) regression with individual features, adjusting for false discovery rates (FDR) and; 2) regression and multivariate analysis of diversity measures; with the possibility of 3) penalized regression or classification approaches (e.g., random forest) for full feature analysis.

Anticipated Period of Performance:

The anticipated period of performance is two years from date of award. Estimated time frame of award is on/about August 2019.

Capability Statement:

Contractors that believe they possess the ability to provide the required services should submit documentation of their ability to meet each of the project requirements to the Contract Specialist.

The capability statement should include 1) the total number of employees, 2) documentation of ability to provide the required equipment, 3) any contractor GSA Schedule contracts by which all of the requirements may be met, if applicable, and 4) any other information considered relevant to this program. Contractors must also provide their Company Name, DUNS number, Physical Address, and Point of Contact Information.

Interested organizations are required to identify their type of business, applicable North American Industry Classification System Code, and size standards in accordance with the Small Business Administration. The government requests that no proprietary or confidential business data be submitted in a response to this notice. However, responses that indicate the information therein is proprietary will be properly safeguarded for Government use only. Capability statements must include the name and telephone number of a point of contact having authority and knowledge to discuss responses with Government representatives. Capability statements in response to this market survey that do not provide sufficient information for evaluation will be considered non-responsive. When submitting this information, please reference the solicitation notice number.

All capability statements sent in response to this Sources Sought Notice must be submitted to Fred Ettehadieh, Contracting Officer, via email at [email protected] before the closing date and time of this announcement. All responses must be received by the specified due date and time in order to be considered.

Note:

This notice does not obligate the Government to award a contract or otherwise pay for the information provided in the response. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After review of the responses received, pre-solicitation and solicitation notices may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. The solicitation release date is pending.