CHISEL: Copy-number Haplotype Inference in Single-cell by Evolutionary Links

CHISEL is an algorithm to infer allele- and haplotype-specififc copy numbers in individual cells from low-coverage DNA sequencing data. Specifically, the current implementation of CHISEL has been designed to be diretly applied to low-coverage DNA sequencing data from 10X Genomics CNV solution, however CHISEL will be adapted to the data generated by any other available technology (e.g. DLP+). CHISEL has been designed and developped by Simone Zaccaria in the group of prof. Ben Raphael at Princeton University. The full description of the algorithm, the comparison with previous state-of-the-art methods, and its application on published cancer datasets are described in the preprint

Simone Zaccaria and Ben Raphael, 2019

The CHISEL algorithm. (A) CHISEL computes RDRs and BAFs in low-coverage (<0.05X per cell) single-cell DNA sequencing data (top left). Read counts from 2000 individual cells (rows) in 5Mb genomic bins (columns) across three chromosomes (grey rectangles in first row) are shown. For each bin in each cell, CHISEL computes the RDR (top) by normalizing the observed read counts. CHISEL computes the BAF in each bin and cell (bottom) by first performing referenced-based phasing of germline SNPs in 50kb haplotype blocks (magenta and green) and then phasing all these blocks jointly across all cells. (B) CHISEL clusters RDRs and BAFs globally along the genome and jointly across all cells resulting here in 5 clusters of genomic bins (red, blue, purple, yellow, and grey) with distinct copy-number states. (C) CHISEL infers a pair of allele-specific copy numbers for each cluster by determining whether the allele-specific copy numbers of the largest balanced (BAF~0.5) cluster are equal to {1, 1} (diploid), {2, 2} (tetraploid), or are higher ploidy. (D) CHISEL infers haplotype-specific copy numbers (a, b) by phasing the allele-specific copy numbers consistently across all cells. (E) CHISEL clusters tumor cells into clones according to their haplotype-specific copy numbers. Here, a diploid clone (light gray) and two tumor clones (red and blue) are obtained. A phylogenetic tree describes the evolution of these clones. Somatic single-nucleotide variants (SNVs) are derived from pseudo-bulk samples and placed on the branches of the tree.


You can download the latest version of CHISEL from the CHISEL GitHub project. The repository includes a detailed documentation, demos, examples, tutorials, guides, and recommentations for usage.


You can ask support and questions about CHISEL on the actively mantained Issues forum of the CHISEL GitHub project](


CHISEL and its applications are described in the following publications:

Simone Zaccaria and Benjamin J. Raphael, Characterizing the allele- and haplotype-specific copy number landscape of cancer genomes at single-cell resolution with CHISEL. bioRxiv (Nov. 10, 2019)