Statement_of_Work_CSI_2019_WES_WGS_RNAseq_CNV.docx

STATEMENT OF WORK (SOW)

TITLE: Genomics services for the NIAID Centralized Sequencing Initiative

1) BACKGROUND INFORMATION

Division of Intramural Research (DIR) scientists study all aspects of infectious diseases, including the causative agent, vectors, and pathogenesis in human and animal hosts. Clinical research is an integral part of this mission, enabling key lab discoveries to be rapidly translated into methods to prevent, diagnose, or treat disease. DIR researchers annually conduct more than 100 clinical trials at the NIH Clinical Center on the Bethesda, Maryland, campus and at collaborating U.S. and international sites. In support of clinical research, DIR has recently authorized a comprehensive initiative to obtain genetic testing results, for all NIAID patients enrolled in clinical trials at the NIH Clinical Center. This is the NIAID Centralized Sequencing Initiative.

2) PURPOSE AND OBJECTIVES OF THE ACQUISITION

The purpose of this acquisition is to support the mission DIR to obtain genetic testing for the NIAID Centralized Sequencing Initiative. The objective is to purchase whole exome sequencing, whole genome sequencing, RNAseq, as well as comparative genomic hybridization microarrays. The centralized sequencing initiative will have direct implications for the care of NIAID patients and for the discovery of the mechanisms of human immunity.

The types of sequencing required for the initiative are; Whole Exome Sequencing (WES), custom microarrays for Comparative Genomic Hybridization (CGH), and Whole Genome Sequencing (WGS) coupled with RNAseq. Exome and genome sequencing allow for discovery of monogenic and polygenic contributions to immune system disorders and CGH microarray sequencing will provide analysis of over 2000 target genes selected by NIAID that cause, or are suspected to cause, immunological diseases in the patient population.

3) CONTRACTOR REQUIREMENTS:

· Whole Exome Sequencing (n = 1750) using the NovaSeq platform:

· Capacity of at least 200 samples per month

· Meets CLIA/CAP requirements for clinical sequencing

· Ability to accept DNA and blood samples

· Consistent batching of samples so that turnaround of batch sent and batch received can be maintained on a rolling basis.

· Sample processing of FASTQ files into BAM/CRAM files and vcf files

· Sequencing read depth of at least 95% at 20X coverage

· SNP trace using Fluidigm for sample identity analysis, assessment of contamination, sex, and relationships with other samples

· Develop and validate probes for deep intronic and UTR variants

· Results returned within 6 weeks

· Whole Genome Sequencing (n = 25) using the NovaSeq platform:

· Sample processing of FASTQ files into BAM/CRAM files and vcf files

· Meets CLIA/CAP requirements for clinical sequencing

· Ability to accept DNA and blood samples

· SNP trace using Fluidigm for sample identity analysis, assessment of contamination, sex, and relationships with other samples

· Minimum sequencing read depth of at least 95% at 20X coverage

· Results returned within 6 weeks

· RNAseq (n = 25):

· >100M reads per sample of total RNA

· FASTQ files and CRAM files

· Results returned within 6 weeks

· Ability to perform sequencing with a rapid turnaround time in special clinical circumstances on up to 25 exomes

· Chromosomal Microarray Analysis (n = 200):

· Sample processing and microarray scanning.

· Feature extraction: Processing of raw image files.

· CNV calls: Use of the vendor’s Genetics pipeline for making copy-number calls from the microarray data.

· Report: Data review by the vendor’s Genetics team for determination of which copy-number calls should be reported clinically. Generation of a report for use by the NIAID team.

· Web-based access to cases and database: Online access for members of the NIAID team to the vendor database of prior results. This is useful for interpretation and clinical reporting.

· Data release of raw image files and any intermediate files upon request.

4) CONTRACTOR SUPPLIED MATERIALS

The Contractor shall provide all consumable reagents except those mentioned below.

5) GOVERNMENT FURNISHED MATERIALS

NIAID will supply DNA (2ug) and RNA patient samples and microarray chips.

6) REPORTING REQUIREMENTS AND DELIVERABLES

The required turn-around time for sequencing (WES, WGS and RNA) is 6 weeks, or less, from the time the contractor receives the patient sample. The requires turn-around time for CGH microarrays is 2 weeks from the time the contractor receives the patient sample.

We also require the vendor to offer a “rapid” 3 week turnaround time (for WES and WGS) from the time the contractor receives the patient sample. This allows for timely return of data to inform patient care at the NIH.

Deliverable format:

FASTQ files, BAM/CRAM files, and vcf files for all samples within 6 weeks. Transfer to occur via cloud-based platform that meets security requirements for transfer to NIH/NIAID servers.

Reports on each sample for use by the NIAID team.

7) INSPECTION AND ACCEPTANCE

All deliverables will be inspected by the project manager, an employee of the Division of Intramural Research. Acceptance will occur when results are successfully transferred to NIH per the specifications and format outline in the requirements above.