attach 1_ metabolon_sow.docx

Statement of Work Metabolomic Profiling of individuals of African Descent with metabolic disorders

Background:

The National Institutes of Health (NIH) mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability. The National Human Genome Research Institute (NHGRI), mission has expanded to encompass a broad range of studies aimed at understanding the structure and function of the human genome and its role in health and disease. A critical part of the NHGRI mission continues to be the study of the ethical, legal and social implications (ELSI) of genome research. The Center for Research on Genomics and Global health (CRGGH) investigates the potential role of genetic and environment factors in the development of complex diseases such as Type 2 diabetes, obesity and hypertension. For more than 20 years, GRGGH has invested in collecting phenotypic data in almost ~6000 + individuals of African descent both in the United States of America and in Africa to close the gap in genetic study inequity (given that the majority of genetic studies to-date has been conducted in population of European ancestry) across populations and to understand health disparity among minority populations.

CRGGH investigators use number of analytical tools to understand the pathophysiology of metabolic disorders. Throughout the years, CRGGH investigators have systematically accumulated different type of -omics data (genomics, transcriptomics, microbiomes) on all or some of our participants with the objective of using integrated analyses to decipher the etiology of metabolic disorders.

Purpose and Objectives:

The purpose of the procurement is to study global metabolomics plus Short Chain Fatty Acid (SCFAs) panel in serum samples of diabetic and non-diabetic individuals of African descent. A subset of the cohort (e.g., East Africans) also has an unexpectedly high circulating triglycerides compared to levels reported in other African populations. Therefore, a secondary objective of this procurement is to compare the metabolic profile of individuals with high triglyceride levels to those with low level of triglycerides. With foresight towards integrating multiple omics analyses in these individuals using outcomes such as metabolic phenotypes including anthropometric markers or clinical biomarkers ascertained during their initial assessment through the Africa America Diabetes study (AADM). The comprehensive scope of metabolomic data required for these analyses includes but is not limited to small molecules metabolites (amino acids, carbohydrates, lipids, nucleotides, energy, cofactors and vitamins, xenobiotics and novel metabolites.) and microbial metabolites namely the SCFAs.

Procurement:

1. The Contractor will conduct global metabolomics (HD4) + SCFA panel on serum samples (n=250) from a subset of AADM participants who also have other -omics data including microbiome. Additionally, 20 samples from 75N92020Q0129 will be used as anchor samples for quality control to merge global metabolomic previously generated and the one that will be generated as part of this requisition. The combined data will be reanalyzed with an overall increase sample size.

2. The contractor will also conduct global metabolomics + fatty acid metabolism panel on a subset of individuals with high and low triglycerides (n=199).

Provided in the Client Data Table format (Excel file).

Turnaround Time from receipt of samples and required information: 9- 13 weeks for Standard Preferred or Supported tubes. 10-14 weeks for Non-Standard tubes.

2.A statistical analysis of the resulting data, which typically consists of univariate significance tests (t-tests, ANOVA, repeated measures analysis, etc.) and, if appropriate, classification analyses.

3.Summary biochemical interpretation of selected, statistically significant metabolites provided in a Word report. An outline of the analytical methods is provided in the report Appendix.

4.Access to the MyMetablon Client Portal for downloading the study deliverables. The MyMetablon Client Portal also provides data analysis and visualization tools that allow for further data exploration.

Turnaround Time from receipt of samples and required information: 9- 13 weeks for Standard Preferred or Supported tubes. 10-14 weeks for Non-Standard tubes.

2. A sample analysis report that includes QC performance information and a table with metabolite concentration results. QC reviewed data can be delivered in advance of the report if requested. No statistics or interpretation will be provided.

Standard Turnaround Time : 6 - 8 weeks from receipt of samples and necessary information.

Additional Service Hours for data merge

Analysis of Lactic acid may be available upon request in selected matrices.

2.A sample analysis report that includes a description of reference chemicals and matrices used during sample analysis, corresponding QC performance information and the data table with sample results. QC reviewed data can be delivered in advance of the report if requested. No statistics or interpretation will be provided.

Standard Turnaround Time: 6 - 8 weeks from receipt of samples and necessary information.

Period of Performance:

Upon award to February 14, 2023

Contract Type:

Firm-Fixed Price

Contractor’s Requirement and Deliverables:

The Government’s minimum requirements are as follows:

· The Contract shall present sufficient capacity to analyze global metabolomics + SCFAs in 250 plasma/serum samples.

· The Contract shall present sufficient capacity to analyze global metabolomics + fatty acid metabolism panel in 199 plasma/serum samples.

· The Contractor shall provide in depth capacity to identify up to several thousand metabolites, known (uniquely named and unnamed)] and high throughput analysis (large sample size analysis) for serum.

· The Contractor shall detect and identify small molecule metabolites of over 60 different chemical classes in plasma/serum.

· The Contractor shall perform no less than four different ultra-high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) methods with peak identification, deconvolution, and chemical intelligence to identify metabolites.

· The Contractor shall compare assessed metabolites to chemical reference library of more than 4,000 known and 8,000 novel metabolites, allowing for rapid and accurate metabolite identification.

· The Contractor shall provide comprehensive named biochemical assayed, known information from public databases (KEGG/HMDB), and relative quantitation of metabolites in each serum sample.

· The Contractor shall provide comprehensive information on unnamed biochemical moieties detected in the global metabolomics and SCFA analyses.

· The Contractor shall destroy all samples 6 months after project completion unless specifically instructed otherwise.

· The Contractor shall provide documentation of the process of generating metabolomics data including internal reference controls and subsample replicates of serum samples provided as well as the raw data generated in the analyses.

· The Contractor shall provide regular written reports and ad hoc conference call updates throughout the analysis process within 10-14 weeks from the receipt of samples for Global metabolomics and within 6 - 8 weeks from receipt of samples and necessary information for SCFA and fatty acid metabolism panel.

Contractor’s Requirement and Deliverables:

The Contractor shall deliver the following:

A- Global metabolomics in plasma/serum samples (mView):

1. The Contractor shall deliver comprehensive metabolite analysis of serum samples derived from four different ultra-high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) methods with peak identification, deconvolution, and chemical intelligence to identify metabolites returning all known and novel metabolites identified by reference libraries.

2. The Contractor shall deliver relative concentration profile of all structurally named small-molecule entities, which can include both endogenous compounds, xenobiotics, and their metabolites, extracted from the samples and detected by HD4 Global Metabolomics platform (Excel file).

3. The Contractor shall deliver data analysis include complex statistical analysis of differential metabolite and content between sample subgroups and comprehensive biochemical association and enrichment analysis in reference biochemical databases (KEGG/HGMD).

4. The contractor shall deliver Summary biochemical interpretation of selected, statistically significant metabolites provided in a Word report. An outline of the analytical methods is provided in Appendix form (Word report).

5. The contractor shall give CRGGH’s investigators access to the MetaboLync ClienPortal for downloading the study deliverables (Word report, Excel data file). TheMetaboLync Client Portal also provides data analysis and visualization tools that allow for further data exploration.

B- Merging Global metabolomics data:

1. The contractor shall merge the global portion of this study with the global portion of 75N92020Q0129 and will be based off 20 anchor samples provided by 75N92020Q0129.

2. The Contractor shall deliver data analysis include complex statistical analysis of differential metabolite and content between type 2 diabetes cases and controls and comprehensive biochemical association and enrichment analysis in reference biochemical databases (KEGG/HGMD).

C- Short Chain Fatty Acid and Fatty acid metabolism Panels:

1. The contractor shall deliver non-GCP absolute quantitation/measurements will be provided for the following analytes for all specimens provided by the client.\

2. A sample analysis report that includes a description of reference chemicals and matrices used during sample analysis, corresponding QC performance information and the data table with sample results. QC reviewed data can be delivered in advance of the report if requested. No statistics or interpretation will be provided.

Place of Contract Performance:

Work will be provided at the Contractor’s site

Government Responsibilities:

· The Government will review monthly written progress report.

· The Government will participate in monthly phone calls for updates.

· The Government will review and approve all invoices.

· The Government will inspect, analyze all samples.

Special Considerations:

Not Applicable

Government Furnished Equipment:

The government will not provide any equipment.