Introduction
PURSUANT TO FAR Subpart 5.2-Synopses of Proposed Contract Actions, THIS IS A PRE-SOLICITATION NOTICE OF A PROPOSED CONTRACT TO ACTION.
THIS IS A PRE-SOLICITATION NON-COMPETITIVE NOTICE OF INTENT TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME).
The National Institute on Drug Abuse (NIDA), Office of Acquisition, Contracts Management Branch Blue, NIA Section on behalf of the National Institute on Aging intends to negotiate and award a purchase order for the Whole metagenomics of the gut microbiome and the brain with the University of North Carolina at Chapel Hill.

North American Industry Classification Systems (NAICS) Code
The intended procurement is classified under NAICS code 541990 - All Other Professional, Scientific and Technical Services with a Size Standard of $15.0 million.

Regulatory Authority
The resultant contract will include all applicable provisions and clauses of the Federal acquisition Regulation (FAR) in effect through the Federal Acquisition Circular (FAC) 2019-03, dated July 12, 2019.

Statutory Authority
This acquisition is conducted as non-competitive under the authority of 41 U.S.C. 253(c) under provisions of the statutory authority of FAR Subpart 6.302-1 -- Only One Responsible Source and No Other Supplies or Services Will Satisfy Agency Requirements.

This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures, Subpart 13.106-1 (b) (1), Soliciting from a single source.

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. The estimated time frame of award is on/about August 2019.

Place of Performance
National Institutes of Health, National Institute on Aging, Baltimore, MD 21224.

Closing Statement
This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice.
Responses to this solicitation must include clear and convincing evidence of the offeror's capability of fulfilling the requirement as it relates to the technical evaluation criteria. The price proposal must include the labor categories, an estimate of the number of hours required for each labor category, fully loaded fixed hourly rate or each labor category, breakdown and rationale for other direct costs or materials, and the total amount. The technical proposal must include CV information for proposed Key Personnel that meet the minimum requirements specified above.
In addition, the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.

A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement.

All responses must be received by the closing date and time of this announcement and must reference the notice number, HHS-NIH-NIDA(AG)-NOI-75N95019R00067. Responses must be submitted electronically to Fred Ettehadieh, Contracting Officer, at [email protected]. U.S. Mail and Fax responses will not be accepted.