Intent to Sole Source Lundquist Institue. VA DNA and medical study support.

The Veteran s Administration (VA) Office of Research and Development, Regional Procurement Office East in Pittsburgh, PA intends to negotiate on a sole source basis with The Lundquist Institute based in Torrance, CA on behalf of the VA Madison, WI VA Healthcare System. The requirement encompasses the development of standard procedures and comprehensive oversight, processing, and analysis of DNA samples for a multisite randomized controlled trial focused on genetic factors influencing blood pressure (BP) and arterial stiffness. The work is to be performed across three study sites: Madison WI, Nashville TN, and Alabama VA facilities. This contract requires the expertise of a specialized team to manage the genetic components of the trial, ensuring the integrity and quality of the genetic data collected. All services requested should be done at one facility to ensure data quality, streamlined data analysis, and to facilitate future analyses. The primary objective is to receive, handle, store, and analyze DNA samples to investigate the potential of a BP polygenic risk score (PRS) in predicting individual responses to BP targets, specifically regarding load-dependent arterial stiffness. This involves the meticulous handling of approximately 250 DNA samples over the contract period, utilizing advanced genotyping techniques and rigorous statistical analysis to identify significant genetic predictors of BP regulation and arterial stiffness. The specific work to be performed includes: Develop manual of procedures for proposed work Receive, store and track packed-cell samples DNA Isolation and Genotyping Genetic analysis and appropriate reporting General consultation and oversight of genetic aspects of the protocol. Task 1 Develop the MOPs for the following Sub tasks: 1) Preparing packed-cell samples for shipping 2) Receiving/handling/storing/tracking of packed cell samples 3) Sample tracking/Barcode/Manifest creation 4) DNA Isolation and Genotyping Subtask 1) Preparing packed-cell samples this MOP will clearly define how samples should be collected, spun down, quantity needed (~7 ml), stored, and batched and packaged prior to shipping including type of tube (plastic EDTA tubes) and back up sample storage procedures. Subtask 2) Receiving/handling/storing of packed cell samples this MOP will present clear and detailed methods of how and where the contractor will receive, handle, and packed cells. Subtask 3) Sample tracking/Barcode/Manifest creation This MOP will present clear and detailed methods of how samples will be tracked and bar coded and an example of the manifest that will be used. Equipment needed at each site (Bar code reader, barcode printer) will be clearly described. Subtask 4) DNA Isolation and Genotyping This MOP will present clear and detailed methods of how DNA will be isolated and genotyped. 1.1 Task 2 Receive, handle, store and track packed-cell samples: Packed-cell samples will be collected from whole blood samples using a standardized protocol in a 7 ml tube at 3 study sites (Madison VA, Nashville VA, and Birmingham VA) throughout the enrollment period. Samples will be spun down and 2 ml of plasma will be removed and stored locally (four 0.5 ml aliquots). Each site will batch and send via overnight shipping on dry ice periodically. These samples will be received, coded for tracking and stored by the contractor at -80 degrees C to ensure sample integrity. The extracted DNA will then be purified and quantified, and aliquots will be stored for future use. If the sample from the baseline visit is inadequate, the onsite study team will be notified, and a second blood sample will be obtained at a subsequent visit and sent for analysis. 1.2 Task 3 - DNA Isolation and Genotyping: Perform DNA isolation and analysis on ~250 samples over 4 years (100 samples in year 1-2 and 50 samples in year 3) using the Global Diversity Array. DNA will be isolated from each sample in a timely manner to ensure sample integrity. GWAS genotyping, we will use the Illumina Infinium Global Diversity Array-8 v1.0 BeadChip (Microarrays | Microarray analysis techniques and products (illumina.com)) which is built on a high-density single nucleotide polymorphism (SNP) global backbone optimized for cross population imputation coverage of the genome. The global diversity array (GDA) human microarray is the most cost-effective variant coverage human microarray from Illumina. It provides targeted coverage of more than 4800 key genes across the genome with approximately 1.8M markers on the BeadChip for high exonic coverage in regions of disease relevance and an average resolution of 1.5Mb. This array enables polygenic risk score development and characterization of genetic architecture in diverse populations. Quality control measures will be employed to ensure that the extracted DNA is of sufficient quality and quantity for downstream analysis. Additional sample and SNP QC, including sample call rate, sample cQC, and sample heterozygosity by ethnicity at the sample level as well as outlier plate checking by call rate, median cQC or heterozygosity at plate level. Cryptic sample duplicates based on IBD/IBS will be dropped. We will exclude monomorphic SNPs across all samples, SNPs with missing rate > 5% or observed heterozygosity > 53%. The DNA will be utilized for GWAS by genotyping using a validated genotyping platform that will be used to identify genetic variants associated with the known blood pressures phenotypes of interest. Stored aliquots will be available for other related DNA technologies, including epigenetics, when funding becomes available. 1.3 Task 4 Genetic analysis: The genotyped data will then be analyzed using standard statistical methods to identify genomic regions associated with the trait of interest. The entire process will be overseen by experienced laboratory personnel at the contractor site to ensure that samples are processed in a timely and efficient manner, and that the data generated is of the highest quality. Characterize the association of blood pressure (BP) polygenic risk score (PRS) with change in stiffness over 12 months. Generalized linear models (GLM) will be used to evaluate the association between PRS (Z-transformed) and change in load-dependent stiffness over 12 months, while adjusting for the risk factors identified in aim 1 and 2, as well as top principle components developed in the population stratification analysis to adjust for potential population stratifications, i.e., Change in load-dependent stiffness over 12 months ~ PRS + PCs + traditional risk factors. The traditional risk factors include all factors established to be associated with load-dependent and structure stiffness, such as age, sex, race, BMI, heart rate, lipids, medications, treatment group. The goal is to identify individuals who will respond best to differences in blood pressure targets in terms of load dependent and structural stiffness. Use generalized linear modeling to evaluate whether BP specific PRS can identify individuals with the greatest changes in load-dependent stiffness over 12 months. In this analysis, changes in load-dependent stiffness over 12 months will be dichotomized as high (>75th percentile) vs. non-high ( 75th percentile). BP specific PRS, treatment arm and the interaction effect between PRS and treatment arm will be included as predictor variables. To determine whether BP PRS can predict changes in load-dependent stiffness independently from BP treatment intensity, the least absolute shrinkage and selection operator (lasso) procedure will be utilized. This procedure will identify a parsimonious model and will determine whether BP PRS is an independent predictor for changes in load-dependent stiffness over 12 months. 1.4 Task 5 General consultation and oversight of genetic aspects of the protocol. The contractor will be available for general consultation and advice regarding all genetic aspects of the protocol. The project requires expert scientific consultation on the interpretation of the resulting data and statistical analysis of the data generated from analyses in order to integrate the findings from each of the measures into a comprehensive evaluation. In addition, the contractor will assist in the formation of presentations and manuscripts to disseminate project results to the public. 2.0 Instructions: The requirement will take place at a VA facility Minneapolis, Minnesota. The sole source is pursuant to FAR 6.302-3 Industrial Mobilization, Engineering, Developmental or Research Capability or Expert Services per 41 USC 3304(a)(3). This notice of intent is not a request for competitive proposals, however; any responsible source who believes it is capable of meeting the requirement may submit a capability statement and supporting documentation to the contracting office no later than Monday, Aug 4, 2025, (10:00 AM, EST). Interest/capability statements may be sent to Michael Haydo at Michael.haydo@va.gov. No telephone responses will be accepted. A determination not to compete the proposed requirement based upon the responses to this notice is solely within the discretion of the Government.