MatchSeq

MatchSeq reconstructs double-stranded DNA fragments at the single-molecule level from single-stranded sequencing data to determine fragment-end structures and molecular damage patterns in ancient, degraded, and cell-free DNA.

Key Features:

• Single-Strand Library Preparation: Uses single-stranded DNA library preparation from diluted DNA samples to enable reconstruction of double-stranded fragments.
• Computational Sequence Matching: Employs computational sequence matching to pair complementary single-strand reads for fragment reconstruction.
• Resolution of Fragment Structures: Resolves blunt ends, 1- or 2-nucleotide overhangs, and single-strand breaks.
• Damage Pattern Identification: Detects short gaps associated with purine loss, cytosine→uracil deamination events, and pyrimidine enrichment in single-stranded regions.
• Application to Complex DNA Sources: Applicable to complex and degraded sources including Neanderthal ancient DNA and cell-free DNA from human blood plasma.
• Reconstruction from Published Data: Reconstructs double-stranded fragments from previously published single-stranded sequence data.

Scientific Applications:

• Ancient DNA Analysis: Reconstructs molecular structures in Neanderthal and other ancient samples to inform paleogenomics.
• Clinical Diagnostics: Analyzes cell-free DNA from plasma for structural and damage signatures relevant to disease diagnosis and monitoring.
• Biochemical Characterization: Characterizes biochemical properties of DNA fragments across biological sources, including patterns of base loss and deamination.

Methodology:

Computationally matches single-stranded reads to identify complementary strands and reconstruct double-stranded fragment sequences and end structures, and identifies purine-loss gaps, cytosine→uracil deamination, and pyrimidine enrichment in single-stranded regions.