NGS-Based Pilot Projects – Sequencing, Bioinformatics, and Analysis

Request for Applications

Purpose and Overview

To advance the cellular and molecular understanding of individualized and population health, undiagnosed diseases, adverse events, and more, the partnership between CTSI and the Mellowes Center for Genomic Sciences and Precision Medicine (MC), is seeking proposals for small-scale research projects that utilize any combination of the genomic, transcriptomic, or epigenomic technologies and bioinformatics platforms available in the MC. Responsive proposals will describe projects that 1) improve our understanding of disease initiation, progression, or therapeutic resistance, 2) show promise to clinically improve disease prevention, early detection, diagnosis or treatment, or 3) develop novel data that empower future studies translating ‘Omics data into the practice.

Thus, responsive projects will be setup to rapidly identify discoveries for better understanding health for our communities through robust, multidisciplinary, and Team Science approaches, that leverage ‘Omics technologies.

Eligibility

• Faculty meeting MCW PI eligibility, or PI eligibility at another CTSI partner, that have an imminently implementable project involving NGS-based methodologies (see MC Technology & Bioinformatics Platforms below).
  • Projects should have a ready hypothesis
  • Sequencing data should meet minimum QC metrics appropriate for the NGS technology.
• Agree to abide by NIH data management sharing policy. (NIH 2023 Data Management Sharing Policy)
• Completion of a 30-minute consultation with the MC ‘Omics technology and bioinformatics team to ensure appropriate allocation of resources and clear communication of project design.  Within one week of consultation, Mellowes Center will provide a statement of work (SOW) with expected timeline and budget.
• Please complete the Pre-application here no later than May 5, 2023.

Number of Awards and Budget

This mechanism will fund up to 4 awards across the following categories in 2023:

• Sequencing through bioinformatics projects will receive up to $15,000 for MC services.
• Bioinformatics-only projects will receive up to $5,000 (approximately 45 hours) for MC services.

Resource Opportunity

Biostatistical, Epidemiology, Research, Design (BERD) mini-grants for biostatistical support are available to applicants for pre- or post-award support. Please see information at Biostatistics, Epidemiology and Research Design (BERD) Mini-grants.

Grant Application Instructions

Link to application will be sent to PI upon completion of the 30-minute MC consultation.

Application Format:

Use standard 11-point font, single space, and half-inch margins throughout the document. Consecutively number all pages.

• Scientific Abstract: Provide a summary of the project (250-word limit).
• Research plan: Provide the aim(s) of the study, background, significance and rationale for the use of NGS-based methodologies and analysis. Describe sample availability (e.g. MCW tissue bank, lab storage), data set(s) to be analyzed (e.g. doi, SRA identifier, or clear file format description), and expected impact of proposed study (3-page limit).
• Future Plans: Provide clear information on how the award will lead to external grant funding (1/2 page limit).
• References. List references cited (not counted in page limit).

Supporting Documentation

• NIH Biographical sketches. Provide an NIH Biosketch in the most current NIH format for each PI and co-investigator.
• Statement of Additional Funding Support.  If initial consultation indicates costs beyond the award amount, include source of additional funds.

Evaluation Criteria and Reporting

Grants will be reviewed by a panel assembled by CTSI and Mellowes Center Leadership, and recommendation for funding made three months following the RFA deadline. Proposals showing promise to support submission of a high-impact paper or a larger proposal for extramural funding will be prioritized.

Awardees will be required to respond to routine post-award surveys and to present their data at a research seminar (to be scheduled by MC).

Timeline

• Pre-applications are due by May 5, 2023.
• Full applications are due by 5:00 pm on June 5, 2023.*
• Recommendation for funding will be made after peer review, by mid-August 2023.
• The start date will be dependent on the status of any required human and animal studies protocol approvals but not later than six months from notification of award. If samples or data are not available within this timeframe, the award will be void.

* Funding Proposals:  applications for this award are not required to be submitted in eBridge. Instead of starting a funding proposal in eBridge, please submit the online REDCap grant application to CTSI by 5:00 p.m. on June 5, 2023. 

Examples of Potential Projects

MC Technology & Bioinformatics Platforms

• DNA-Based testing
  • Sample types include frozen cell pellets, flash-frozen tissue, isolated total DNA
  • Tumor and/or somatic variant calling and analysis
  • Germline variant calling and analysis for cancer patients to investigate etiology or predisposition
  • Differences in variant (SNV, MNV, INDEL, CNV) frequencies between cases and controls
  • Analysis of specific inheritance patterns among duos, trios, or quads
• RNA-Seq differential expression analysis (bulk, low input or single cell analysis available)
  • Sample types include frozen cell pellets, flash-frozen tissue, isolated total RNA (from 10pg to 1ug), single cell preparation
  • Differential expression by pairwise conditions or among groups of conditions/phenotypes
  • Results summary via PCA (dimensionality reduction), volcano plot, heatmaps, and pathway analysis
• DNA accessibility profiles via ATAC-Seq
  • Sample type includes lifted and pelleted cells (at approximately 100,000 cells per condition)
  • Report on genome-wide patterns of peak position and intensity differences
  • Summary on genes and their proximal regulatory regions
• DNA CpG Methylation via RRBS or EPIC methylation arrays
  • Sample types include frozen cell pellets, flash-frozen tissue, isolated DNA (150ng – 1ug)
  • Global profile summaries, CpG calling and quantification, region-based quantification (tiling or DMRs), annotation with TFs and/or marks
  • Differential CpG and DMR calling among conditions
  • Summary of genes and their proximal regulatory regions with altered methylation
• Histone-based ChIP-Seq and/or cut-and-run
  • Actively growing tissue culture cells, fixed cell pellet (consultation available regarding method of fixation and total numbers needed) or prepared library
  • Report on genome-wide patterns of peak position and intensity differences
  • Summary on genes and their proximal regulatory regions

Project Example Workflows Across CTSI and MC

We provide the below examples, as practical examples for how investigators can combine expertise from our two organizations, to pursue novel research studies at MCW.

• Clinician Researcher studying demographics of cardiovascular disparities​ with an interest in biologic factors that mediate impact​
  • Study design, data or samples available with PI or core facility
  • Consult + RNA-Seq on immune cells (MC)​
  • Bioinformatics of NGS data (MC)​
  • Population or Epidemiology links (CTSI)
• Clinical Trial to look at a new intervention, with data that indicates hepatic toxicities and PI anticipates it’s related to gene regulation in the tissue
  • Sample acquisition and storage (Tissue Bank)
  • Histopathology report (PML)
  • Consult + RNA-Seq + ChIP-Seq on dissected tissues (MC)
  • Bioinformatics of NGS data (MC)
  • Population or Epidemiology links (CTSI)
• Basic Researcher studying a specific cytokine’s effect​ with an interest in how these cytokines differently regulates other cell types​
  • Study design, data or samples available with PI or core facility
  • Consult + RNA-Seq on cells exposed to the cytokine w & w/o stimulation (MC)​
  • Bioinformatics (MC)​
  • Population or Epidemiology links (CTSI)

Reporting

As an NIH supported program, the CTSI is required to collect benchmark, annual progress, and long-term outcomes reports of all Pilot awarded projects. Timely progress and reporting of the funded research project is a requirement of the award.

These CTSI Pilot – Mellowes Center Awards are funded by the Medical College of Wisconsin (MCW). All applications and awarded projects must follow respective processes including but not limited to reporting requirements.

Funding Acknowledgement

Please acknowledge the National Institutes of Health (NIH) CTSA award when publishing or presenting any outcomes resulting from your study by including the CTSI Funding Acknowledgement.

Questions?

Please contact Renee McCoy, CTSI Pilot Award Program Director, at rmccoy@mcw.edu.