CLImAT: accurate detection of copy number alteration and loss of heterozygosity in impure and aneuploid tumor samples using whole-genome sequencing data.
BACKGROUND
Whole-genome sequencing of tumor samples has been demonstrated as an efficient approach for comprehensive analysis of genomic aberrations in cancer genome. Critical issues such as tumor impurity and aneuploidy, GC-content and mappability bias have been reported to complicate identification of copy number alteration and loss of heterozygosity in complex tumor samples. Therefore, efficient computational methods are required to address these issues.


RESULTS
We introduce CLImAT (CNA and LOH Assessment in Impure and Aneuploid Tumors), a bioinformatics tool for identification of genomic aberrations from tumor samples using whole-genome sequencing data. Without requiring a matched normal sample, CLImAT takes integrated analysis of read depth and allelic frequency and provides extensive data processing procedures including GC-content and mappability correction of read depth and quantile normalization of B-allele frequency. CLImAT accurately identifies copy number alteration and loss of heterozygosity even for highly impure tumor samples with aneuploidy. We evaluate CLImAT on both simulated and real DNA sequencing data to demonstrate its ability to infer tumor impurity and ploidy and identify genomic aberrations in complex tumor samples.


METHODS
The CLImAT software package can be freely downloaded at http://bioinformatics.ustc.edu.cn/CLImAT/.
School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China.
Zhenhua
Z
Yu
School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China.
Yuanning
Y
Liu
School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China.
Yi
Y
Shen
School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China.
Minghui
M
Wang
School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China School of Information Science and Technology and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei AH230027, China.
Ao
A
Li
D000782:Aneuploidy; D056915:DNA Copy Number Variations / Q000235:genetics*; D005787:Gene Frequency; D023281:Genomics / Q000379:methods*; D006801:Humans; D019656:Loss of Heterozygosity; D017422:Sequence Analysis, DNA; D012984:Software; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*