Micro-C Genomics Services

Requirements: 1. Purpose Dovetail Genomics LLC Micro-C service employs micrococcal nuclease (MNase) digestion to generate highly uniform fragments, enabling precise capture of nucleosome positioning with even genomic coverage. This approach provides increased mapping resolution at the nucleosome level, while proximity ligation data enriched for long-range informative reads allows detection of higher-order chromatin organization, including chromatin loops and interaction frequencies. The purpose of this Statement of Work is to acquire Dovetail Genomics LLC Micro-C services for samples processing and associated data generation in support of NCI/CCR/LRBGE research on the effects of substrate stiffness on 3D chromatin architecture in colon cancer cell lines. This information will allow us to better understand the impact of substrate stiffness on gene regulation and cancer cell behavior. 2.

Background Mechanical cues regulate cell behavior in development, regeneration, aging, and disease, and in colon cancer, extracellular matrix stiffening may promote malignancy by altering focal adhesions, YAP1 transcription factor activity, invasion, transcriptional programs, and nuclear organization. Given the rising incidence of colorectal cancer in young adults and the NIH emphasis on human-based, animal-free research models, we will compare human colon cancer cells grown on substrates of different stiffnesses to determine whether physiologically relevant soft hydrogels, compared with rigid plastic, alter 3D nuclear architecture assessed by Micro-C. This work will test whether matrix stiffness reshapes chromatin organization and mechanosensitive transcriptional responses in ways that may be missed in conventional culture, supporting more predictive human-based models for cancer biology research. Although third-party service contractors may theoretically offer related sample-processing support, they would not provide the same Dovetail Genomics LLC quality micro-C data and may be more expensive while not delivering the same analysis, comparability, or direct platform support required for this project. 3. Scope The Contractor shall provide Dovetail Genomics LLC Micro-C Service and analysis for 8 Government-provided samples. Services shall include receipt and accessioning of submitted samples, processing using the Dovetail Genomics LLC protocol, applicable quality control steps, generation of analytical output, delivery of data files and summary documentation, and technical support needed to interpret the generated data within the scope of the quoted service. 4. Contractor

Requirements and Tasks Task 1: Project initiation and sample logistics. Coordinate with the Government technical

point of contact to confirm sample submission

requirements, sample manifest format, shipping instructions, acceptance criteria, and anticipated processing schedule before samples are shipped. Task 2: Sample receipt and accessioning. Receive Government-provided samples; verify submitted samples against the Government-provided manifest; notify the Government of any discrepancies, insufficient volume, labeling concerns, shipping deviations, or conditions that may affect assay performance. Task 3: Olink Explore HT sample processing. Process accepted samples using the Dovetail Genomics LLC Micto-C Service workflow in accordance with Dovetail Genomics LLC standard operating procedures and applicable quality standards. The Contractor shall use the Dovetail Genomics LLC platform, associated proprietary reagents, workflow, and analysis processes required to generate the requested Micro-C data. Task 4: Quality control and data review. Perform applicable assay, sample, and data quality control review. The Contractor shall identify failed samples, quality-control flags, batch concerns, or other limitations relevant to interpretation of the analytical results. Task 5: Data delivery. Provide the Government with the data generated from the Dovetail Genomics LLC Service, including supporting files/customary documentation provided with the service.

Deliverables shall be provided electronically to the Government technical