ArCH

ArCH integrates outputs from multiple variant callers and applies sequencing-error–aware filtering to detect clonal hematopoiesis (CH) somatic variants at low allelic fractions for study of clonal expansion and hematologic risk.

Key Features:

• Comprehensive Variant Calling Pipeline: Integrates outputs from four distinct variant calling tools and applies filtering based on variant characteristics and estimated sequencing error rates to improve sensitivity and accuracy.
• Scalable Processing and Input Flexibility: Supports scalable cloud-based processing, a range of input formats, and customizable parameters to accommodate diverse sequencing technologies and datasets.
• Enhanced Sensitivity and Positive Predictive Value: Validated using deep targeted sequencing from acute myeloid leukemia patient samples, technical replicates, and blood samples with orthogonal validation to improve detection of low-allele-frequency CH variants.
• Reproducibility and Validation: Provides a validated, reproducible pipeline that produces consistent variant calls across different datasets.

Scientific Applications:

• Hematologic Research: Enables mapping of clonal trajectories over time to study clonal hematopoiesis progression and its relationship to hematologic malignancies.
• Clinical Diagnostics: Detects low-frequency CH mutations for early diagnosis and risk assessment in patients predisposed to blood cancers.
• Genomic Studies: Facilitates large-scale genomic studies of the genetic underpinnings of hematopoietic disorders by providing reliable CH variant detection.

Methodology:

Data integration by combining outputs from multiple variant calling tools; error filtering using sequencing error rate estimation and variant characteristic analysis; and parameter customization to tailor calls to specific datasets.