Attachment-SOW DNA methylation 1.5.21_ll.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Discovering differential DNA methylation patterns in Alzheimer's disease and related disorders in a large population based cohort:AGES-RS

Statement of Need and Purpose:

Alzheimer‘s disease (AD) is devastating and global public health problem with an urgency to identify public health interventions and therapeutics. Although we now understand the disease to be a complex integration of disease pathways and risk factors, our understanding of the causal chain of events remains elusive. However, recent advances in technology provide us with new opportunities to identify genetic, environmental and gene-environment interactions that play a role in disease causation.

One such discovery is the role of the epigenome, an intermediary between genetic and environmental interactions that can contribute to the risk of complex disease (Lin et al., 2018;

Qureshi & Mehler, 2015). The epigenome modulates cell- and tissue-specific gene expression, and is also affected by nongenetic risk factors, smoking being a well established modulator of the epigenome. Ultimately, the epigenome can change gene and protein expression, and alter the vulnerability to disease (Hannon, Lunnon, Schalkwyk, & Mill, 2015; Lin et al., 2018; van Dongen et al., 2016) (Gao, Jia, Zhang, Breitling, & Brenner, 2015; Marioni et al., 2018).

Thus, there is a critical need to better understand the pathobiology of, and identifying candidate interventions against AD, by characterizing the methylation patterns consistent with AD dementia and related cognitive and brain imaging biomarkers (Bpath).

Background Information and Objective:

Understanding the brain remains one of the 21st century’s greatest challenge. There has been some progress in identifying genes that regulate the normal development of the brain, as well as the abnormal development of pathology that effects a wide range of system dysfunction. The AGES-RS cohort has already been well characterized with genomics and proteomics. The addition of data on the epigenome will enhance the value of this cohort with the broad objective of identifying risk factors for and mechanisms underlying AD.

Infinium MethylationEPIC provides robust methylation profiling microarray with extensive coverage of CpG islands, genes, and enhancers. The array can interrogate over 850,000 methylation sites quantitatively across the genome at single-nucleotide resolution. Multiple samples, including FFPE, can be analyzed in parallel to deliver high-throughput power while minimizing the cost per sample. Furthermore, Infinium HD array technology enables content selection independent of bias-associated limitations often associated with methylated DNA capture methods.

Period of Performance:

The period of performance is for one year, with an anticipated start date of March 1st, 2021 thru February 28th, 2022.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work.

Specific Requirements:

Perform methylation analyses of 5000 samples from 2500 individuals with 2 timepoints, of DNA samples, who were examined in AGES 1 and 2.

Plate out DNA to account for batch effects on the 2 time point within individual comparisons.

Identify a Lab that uses a methylation platform [Illumina Infinium MethylationEPIC BeadChip array] consistent with data from other large studies so that the results from AGES is suitable for pooled analyses.

Provide a sample tracking sheet to be sent to the Laboratory that performs the methylation assays.

The methylation platform should be consistent with data from other large studies so that the results from AGES is suitable for pooled analyses.

Obtain data in electronic form that includes methylation (CPG) sites and are quality controlled and normalized to a given standard.

Process and conduct analyses to demonstrate the integrity of the data and to investigate associations of methylation patterns to cross-sectional and longitudinal change in brain pathology.

Send a report to NIA Program Officer.

LEVEL OF EFFORT:

Staff sufficient to organize shipment of 5,000 DNA samples to the Laboratory; to receive the completed and normalized data; and to process the data for integrity checks and associations with brain pathology. One analyst, 12 months on project.

GOVERNMENT RESPONSIBILITIES

Provide adequate funding to support efforts to obtain valid and processed methylation data.

DELIVERY OR DELIVERABLES

MS Excel files with AGES-RS ID and DNA methylation values for 5,000 DNA samples. A report on the analysis results including quality of the data will be delivered electronically within 12 weeks of receipt of the samples. Specific files should include:

• Raw data files, containing the intensity iDAT files

• Normalized data

• Sample tracking sheet

• QC report files in xml format, with appendix file in txt format.

REPORTING REQUIREMENTS

The final report should include quality measure of each methylation value, overall non-detection rate, coefficient of variation of the measures, batch effects, any data needed for future standardization and pooling with other data, normalization procedures, etc.

OTHER CONSIDERATIONS

Travel:

No travel required.

Key Personnel:

One analyst for 12 months who can oversee the appropriate shipping of the samples to the designated Lab; monitor progress in completion of the assay work;, receive the data back, integrate data into the AGES data archive, check for the integrity of the data and write a final report for NIA.

Information System Security Plan:

N/A

Data Rights:

The National Institutes on Aging shall have unlimited rights to and ownership of all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General, ” is hereby incorporated by reference and made a part of this contract/order.

Section 508—Electronic and Information Technology Standards:

The contractor shall comply with Section 508 of the Rehabilitation Act (29 U.S.C. § 794d), as amended by the Workforce Investment Act of 1998 (P.L. 105-220), August 7, 1998.

Publications and Publicity:

No publications required.

Confidentiality of Information:

Data will be deidentified.