EpiVIA
EpiVIA performs joint profiling of chromatin accessibility and lentiviral CAR-T cell integration sites to map chromatin state and vector insertion at population and single-cell resolution.
Key Features:
- Chimeric read parsing: Parses sequencing reads to identify chimeric fragments resulting from lentiviral vector integration into the host genome.
- Combined reference alignment: Classifies fragments based on alignment patterns to a combined host-plus-viral reference genome.
- Single-cell integration and accessibility mapping: Determines chromatin accessibility and precise CAR-T vector integration sites at single-cell and population levels.
- Host and viral genome mapping: Maps both host and viral genomic sequences to localize integration breakpoints and accessible chromatin regions.
- Validation on clonal cells: Validated using clonal cells with known integration sites to assess accuracy of lentiviral integration detection and chromatin accessibility measurement.
Scientific Applications:
- CAR-T integration site analysis: Identifies precise lentiviral insertion sites of CAR constructs within T cells to study insertional patterns.
- Chromatin accessibility profiling: Profiles accessible chromatin regions concomitant with integration to assess the regulatory context of insertions.
- Assessing effects on T cell regulation: Enables investigation of whether CAR construct integration alters regulatory landscapes that affect T cell proliferative competence.
- Mechanistic studies of CAR-T efficacy: Facilitates mapping of host gene regulation and cellular factors associated with durable responses following CAR-T therapy.
Methodology:
Parses sequencing reads to identify chimeric host–viral fragments, aligns fragments to a combined host-plus-viral reference genome, classifies alignment patterns to assign integration breakpoints, and maps chromatin accessibility and vector insertion sites at single-cell resolution.
Topics
Details
- Tool Type:
- command-line tool
- Programming Languages:
- Python
- Added:
- 1/18/2021
- Last Updated:
- 3/8/2021
Operations
Publications
Wang W, Fasolino M, Cattau B, Goldman N, Kong W, Frederick MA, McCright SJ, Kiani K, Fraietta JA, Vahedi G. Joint profiling of chromatin accessibility and CAR-T integration site analysis at population and single-cell levels. Proceedings of the National Academy of Sciences. 2020;117(10):5442-5452. doi:10.1073/pnas.1919259117. PMID:32094195. PMCID:PMC7071901.