HBOS-CNV: A New Approach to Detect Copy Number Variations From Next-Generation Sequencing Data

Abstract

Copy number variation (CNV) is a genomic mutation that plays an important role in tumor evolution and tumor genesis. Accurate detection of CNVs from next-generation sequencing (NGS) data is still a challenging task due to artifacts such as uneven mapped reads and unbalanced amplitudes of gains and losses. This study proposes a new approach called HBOS-CNV to detect CNVs from NGS data. The central point of HBOS-CNV is that it uses a new statistic, the histogram-based outlier score (HBOS), to evaluate the fluctuation of genome bins to determine those of changed copy numbers. In comparison with existing statistics in the evaluation of CNVs, HBOS is a non-linearly transformed value from the observed read depth (RD) value of each genome bin, having the potential ability to relieve the effects resulted from the above artifacts. In the calculation of HBOS values, a dynamic width histogram is utilized to depict the density of bins on the genome being analyzed, which can reduce the effects of noises partially contributed by mapping and sequencing errors. The evaluation of genome bins using such a new statistic can lead to less extremely significant CNVs having a high probability of detection. We evaluated this method using a large number of simulation datasets and compared it with four existing methods (CNVnator, CNV-IFTV, CNV-LOF, and iCopyDav). The results demonstrated that our proposed method outperforms the others in terms of sensitivity, precision, and F1-measure. Furthermore, we applied the proposed method to a set of real sequencing samples from the 1000 Genomes Project and determined a number of CNVs with biological meanings. Thus, the proposed method can be regarded as a routine approach in the field of genome mutation analysis for cancer samples.

ncRNAs-mediated high expression of TICRR promotes tumor cell proliferation and migration and is correlated with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

“…SCNA and gene mutation play critical roles in tumorigenesis and development. 25 , 26 , 27 The mutation frequency of liver cancer was only approximately 0.5%, while the arm-level deletion, diploid/normal, and arm-level gain were major types of variation. The high rate of SCNV had a better prognosis.…”

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“…Con relación a CNV, consisten en encontrar en el alineamiento de la biblioteca de secuenciación un exceso (inserciones) o defectos (deleciones) de nucleótidos 59 the histogram-based outlier score (HBOS. En los reordenamientos o rearreglos están incluidas translocaciones e inversiones entre otras, que llevan a que se fusione la totalidad o parte de dos genes.…”

A Bioinformatics Toolkit for Next-Generation Sequencing in Clinical Oncology

“…Biol. 2023, 45 9740 CNV calling CNV-LOF, CoverageMaster, CNV-RF, DeepCNV, CNV_IFTV, HBOS-CNV, CNV-MEANN, ControlFREEC, ifCNV *, mcna [42][43][44][45][46][47][48][49][50][51] MSI status calling MIAmS *, MSIsensor, MSIdetect, deltaMSI [52][53][54][55] * Used in our in-house bioinformatics pipeline.…”