Investigating the Biology of Cognitive Resilience in WHIMS - APOE e4 Escapees using machine learning

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. Statement of Need and Purpose: In the proposed study we will apply advanced machine learning methods to the analysis of proteomics and metabolomics data from the Women's Health Initiative Memory Study (WHIMS). We will compare APOE e4 carriers with and without cognitive impairment to determine the unique profiles of metabolites and proteins that may render women with an APOE e4 allele resistant to subsequent impairment. We will determine whether the profiles of metabolites and proteins are specific to e4 carriers or also distinguish between e3/e3individuals with and without cognitive impairment. The primary two aims are: a) To examine whether differences in biomarker profiles exist among APOE e4 women who are cognitively resilient compared to those who are not. b) To examine whether these differences vary from those seen among e3/e3 women. We will also investigate groups of women with and without the APOE e4 allele who develop cognitive impairment at age 80 and older to allow us to also compare age-matched women with and without cognitive impairment. Background Information and Objective: The APOE e4 allele is the most robust genetic risk allele for late onset Alzheimer's disease (AD) and is associated with a 3 to 4-fold increase in risk and an earlier onset of cerebral amyloid accumulation. Carriers of the e4 allele are also at increased risk for cardiovascular disease, and mortality. However, carriage of an APOE e4 allele or even two copies of the e4 allele is not sufficient for the development of AD and many e4 carriers survive to old age without developing cognitive impairment. Individuals who survive to old age and maintain cognitive health despite the presence of one or two APOE e4 alleles provide a unique opportunity to better understand the demographic, health, behavioral and physiologic characteristics associated with cognitive resilience. WHIMS investigators are currently investigating demographic, health and lifestyle characteristics of cognitive resilience in APOE e4 carriers but physiologic studies that may provide greater mechanistic insights are lacking. The aim of the WHIMS Resilience proposal is to utilize the unique expertise and resources of the NIA Intramural Research Program (IRP) in a coordinated multi-laboratory project to perform deep phenotyping and identify potential physiologic characteristics that promote cognitive resilience. In the WHIMS cohort we have identified 709 women who have APOE e3/e4 (n= 654) or e4/e4 (n=55) genotypes. Of these women, 350 have survived beyond age 80 and remain free of cognitive impairment, 115 developed cognitive impairment at age 80 and younger, and 244 developed cognitive impairment after age 80. We have used biospecimens collected at Women's Health Initiative (WHI) baseline (~20 years ago) to compare the 350 women who remain free of cognitive impairment after age 80 despite carrying an APOE e4 allele with the 115 e4 carriers who developed cognitive impairment at age 80 and younger and with the age comparable sample of women who developed cognitive impairment after age 80. In addition, to determine whether any identified protective factors are specific to e4 carriers, similar comparisons will be evaluated for women with e3/e3 genotypes who survive and are free of impairment beyond age 80 with those who develop impairment at age 80 and younger and those who develop impairment after age 80. Alzheimer's disease biomarkers, proteomic and metabolomic assays have been completed. The goal of this proposal is to support the application of advanced statistical methods, using machine learning, to the completed assay data to accomplish the aims of the overall project. Project Requirements/Salient Characteristics: Apply machine learning methods to the analysis of proteomics and metabolomics data. 1.Perform classification analyses to evaluate the capability of proteomics to discriminate between WHIMS women who are APOE ?4 carriers according to cognitive resilience status. Determine multivariate proteomics signatures predictive of cognitive resilience. 2.Perform classification analyses to evaluate the capability of proteomics to discriminate between WHIMS women who carry APOE genotype ?3/?3 according to cognitive resilience. Determine multivariate proteomics signatures predictive of cognitive resilience. 3.Perform survival analyses of incident cognitive impairment using all the available data. Metabolomics Analyses 4. Similar analyses as described in 1-3. Combined Analyses 5. Similar analyses as described in 1-3 but based on the concatenation of all markers (proteins, metabolites and blood biomarkers of Alzheimer's disease). 6. Similar analyses as described in 1-3 but based on concatenating blood AD biomarkers with proteomics and metabolomics signatures determined independently during training. Anticipated Period of Performance: 11/1/2021 - 9/30/2022 Other Considerations: Key Personnel- Ph.D. with experience in advanced machine learning approaches, biostatistics, neuroimaging, metabolomics and proteomics. Contractor must have access and familiarity with WHIMS/WHI database. Capability Statement/Information Sought: Respondents must provide, as part of their responses, a capability statement clearly identifying their ability to provide the requested service. The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2 x 11 paper size, with 1 top, bottom, left and right margins, and with single or double spacing. 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