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.

PMID: 32094195
PMCID: PMC7071901
Funding: - Office of Extramural Research, National Institutes of Health: R01HL145754