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Development and Improvement of Research Software for DNA Methylation and RNA Sequencing Analysis

Award Number: R50CA305793
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Development and Improvement of Research Software for DNA Methylation and RNA Sequencing Analysis - Project Summary I am a research software engineer in Dr. Hui Shen’s laboratory at the Van Andel Institute (VAI), where we focus on the origin of cancer through DNA methylation and single-cell technologies. I am currently supported by Dr. Shen’s ESI MERIT award (R37CA230748) and a cooperative agreement for the Genomic Data Analysis Center's Integrative Cancer Epigenomic Data Analysis Center (U24CA264023) from the NCI, as well as a Commons Fund Award (UM1DA058219). As part of these efforts, I develop standards-compliant tools that work across a wide spectrum of inputs. For example, I developed or co-developed BISCUIT, biscuiteer, dupsifter, and bisplotti – tools for analyzing whole genome bisulfite sequencing (WGBS) and WGBS-like data. BISCUIT and dupsifter are available on bioconda and have been downloaded a combined >23,700 times, while biscuiteer is available on Bioconductor and has been downloaded >9,000 times by >2,700 unique IP addresses. I worked with the original STORM-seq technology developers (at VAI and Takara Bio) and developed a quality control (QC) pipeline for detecting and mitigating contamination from adapter oligonucleotides, missed plate wells during cell sorting, and failed ribo-depletion. In addition, I developed a pipeline for adding an in silico barcode to each read and aligning STORM-seq data to a reference genome. All my tools are well-documented in detailed GitHub repository README files, R Markdown vignettes, or static websites. In this R50 project, I will support Dr. Shen’s projects by removing unused code from BISCUIT, improving the speed which DNA methylation information is extracted from aligned BAMs, and creating a testing framework. I will simplify dupsifter by re-coding how the two bisulfite strands are delineated and add functions for differentiating unique molecular indexes (UMIs) in the duplicate read signature. For the RNA-seq tools, I will add new STORM-seq QC metrics and a function for including cell barcodes and UMIs simultaneously. For my independent R50 research projects, I will develop new tools for analyzing thousands of WGBS samples across multiple tissues from the Sequencing Read Archive (SRA) and identifying conserved hyper- and hypo-methylated regions. I will also develop a tool that reads raw FASTQ files and filters out potential strand invasion events that occur when using template switching oligonucleotides during reverse transcription or RNA-RNA interaction events. These chimeric reads can affect downstream analysis through improper collapsing of UMIs or misidentifying RNA-RNA interactions as structural variants. Through this R50 award, I will complete my MS in software engineering; grow my understanding of data compression techniques; apply that knowledge to store and manipulate large biomedical datasets; and apply formal software engineering principles to the tools that I develop, thus establishing myself as a high-quality research software engineer at VAI, and for the larger research software field.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $190,764 )
2026	2026	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Cancer Biology Research	000	1	8/31/2026	NEW	$190,764
														Subtotal = $190,764

Grand Total All Awards = $190,764

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Development and Improvement of Research Software for DNA Methylation and RNA Sequencing Analysis

Award Number: R50CA305793

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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