Whole genome sequencing for investigation of age-related chronic disease in HANDLS participants

Investigators in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study require whole genome sequencing (WGS) processing to expand our current research examining whether genetic variants contribute to age-related chronic diseases. Samples from HANDLS participants have been collected over 20 years and many are over 10 years old. A contract is required because the Government does not have available facilities or resources to perform this work consistent with other WGS performed on other HANDLS samples.

The objective of this work is expanding our current research to examine health differences associated with age-related chronic diseases through whole genome sequencing to investigate the contributions of genomics to the burden of disease incidence, prevalence, morbidity, and mortality in populations within the United States. The long-term goal is to create a consistent dataset of whole genome sequencing to complement the longitudinal HANDLS behavior and health data.

The contractor will deliver plates to the Government sufficient to run 600 samples, some of which have been stored for ten or more years. The contractor will perform whole genome sequencing, and specifically shall:

• Sequence libraries on the NovaSeq X-Plus platform with 25B-300 flow cells using 150 bp paired end runs and NovaSeq workflow-series 10B sequencing run
• confirm genomic DNA quantity and quality by performing DNA concentration measurements and volume checks
• Re-attempt sequencing in the case that DNA quality and quantity is sufficient, but sample fails sequencing-based quality control
• Examine agarose gels on all samples as an industry-standard method for screening DNA marker quality prepare PCR-free sequence libraries for all samples
• Sequence the libraries at a minimum of 30x coverage with 2×150 base pair runs
• Perform primary and secondary analysis of the sequencing data including but not limited to read alignment, variant calling, and quality control analyses
• Quality control checks will include confirming sex, identifying unexpected duplicates and relatedness, confirming relatedness, providing sample performance information and sample identity confirmation against the sequencing data, in addition to confirming coverage, contamination, mapped reads, and other general quality metrics.
• Alignment and variant calling will be performed with the DRAGEN Germline pipeline. After quality is confirmed, joint variant calling should be performed producing a multi-sample VCF file.
• Provide written summaries and documentation of the methods used to perform the whole genome sequencing pipeline
• Supply the whole genome sequencing data in a mutually acceptable electronic format that preserves study participants’ confidentiality. Data delivered will include:
  • per sample CRAMs
  • per sample gVCFs
  • per sample VCFs
  • joint-called multi-sample VCF
  • per sample structural variant and CNV calls
  • QC report and data dictionary
  • Sample manifest with flagged problems

Following data delivery and upon request by the Government, the contractor shall provide attendance at Government laboratory staff meetings, and the contractor shall provide technical consultations as needed. The contractor will also ship overnight on dry ice any leftover samples on plates to the Biomedical Research Center in Baltimore, MD.

Please refer to the attachments for complete details, specifications and relevant information.