HomSI: a homozygous stretch identifier from next-generation sequencing data

Gormez, Zeliha; Bakir-Gungor, Burcu; Sağıroğlu, Mahmut Şamil

doi:10.1093/bioinformatics/btt686

Cited by 39 publications

(24 citation statements)

References 13 publications

(14 reference statements)

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“…With rapidly decreasing costs and increasing throughput of NGS technologies, it became attractive to apply homozygosity mapping directly on whole-exome sequencing (WES) data, without the need of prior SNP genotyping. Several computer programs have recently been developed or adapted to assist in ROH identification of WES data, including GERMLINE, 6 AgileGenotyper/ AgileVariantMapper, 7 HomSI, 8 HomozygosityMapper, 9 and H 3 M 2 , 10 each of which demonstrates specific limitations. Lower performance of the GERMLINE algorithm in comparison to PLINK 11 and BEAGLE has been shown for SNP arraybased ROH analysis.…”

Section: Introductionmentioning

confidence: 99%

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Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing

Kancheva

Atkinson

Rijk

et al. 2016

Genetics in Medicine

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Purpose: Homozygosity mapping is an effective approach for detecting molecular defects in consanguineous families by delineating stretches of genomic DNA that are identical by descent. Constant developments in next-generation sequencing created possibilities to combine whole-exome sequencing (WES) and homozygosity mapping in a single step. Methods:Basic optimization of homozygosity mapping parameters was performed in a group of families with autosomal-recessive (AR) mutations for which both single-nucleotide polymorphism (SNP) array and WES data were available. We varied the criteria for SNP extraction and PLINK thresholds to estimate their effect on the accuracy of homozygosity mapping based on WES.Results: Our protocol showed high specificity and sensitivity for homozygosity detection and facilitated the identification of novel mutations in GAN, GBA2, and ZFYVE26 in four families affected by hereditary spastic paraplegia or Charcot-Marie-Tooth disease. Filtering and mapping with optimized parameters was integrated into the HOMWES (homozygosity mapping based on WES analysis) tool in the GenomeComb package for genomic data analysis. Conclusion: We present recommendations for detection of homozygous regions based on WES data and a bioinformatics tool for their identification, which can be widely applied for studying AR disorders. Genet Med advance online publication 22 October 2015Key Words: Charcot-Marie-Tooth neuropathy; hereditary spastic paraplegia; homozygosity mapping; PLINK; whole-exome sequencingThe last two authors shared coauthorship. The first two authors and the last two authors contributed equally to this work.

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Section: Introductionmentioning

confidence: 99%

“…A similar graphical output is created by HomSI. 8 Both AgileGenotyper/AgileVariantMapper and HomSI were able to retrieve the homozygous regions containing the diseasecausing mutations from WES data. Nevertheless, their output data requires visual inspection and subjective interpretation.…”

Section: Introductionmentioning

confidence: 99%

Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing

Kancheva

Atkinson

Rijk

et al. 2016

Genetics in Medicine

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“…Using HomSI algorithm [22], the WES data were analyzed for region specific increased ratio of homozygous variants.…”

Section: Methodsmentioning

confidence: 99%

Multifocal gastric adenocarcinoma in a patient with LRBA deficiency

Bratanič

Kovač

Pohar

et al. 2017

Orphanet J Rare Dis

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BackgroundLipopolysaccharide-responsive, beige-like anchor protein (LRBA) deficiency is characterized by primary immunodeficiency and autoimmunity. Cancer may present another feature of LRBA deficiency. We describe a case history of a young adult with LRBA deficiency and two independent malignancies.MethodsFamily-trio whole exome sequencing with unbiased phenotype ontology approach was used for identification of causative mutations of a primary immune deficiency disorder. Additionally, we sought to identify germline mutations in genes known to be associated with two independent malignancies using a targeted approach. A cytotoxic T-lymphocyte associated protein 4 (CTLA4) expression in T lymphocytes was determined by flow cytometry.ResultsIn the patient with clinical signs of LRBA deficiency multifocal gastric carcinoma and malignant melanoma were diagnosed and surgically treated at 19 and 27 years of age, respectively. Despite refusal of any adjuvant chemotherapy or radiotherapy, the patient demonstrated disease free survival for at least 13 years after the first cancer diagnosis. A homozygous frameshift deletion in LRBA gene (p.Glu946Ter) and two common variants in TYR gene were identified. Reduced CTLA4 expression in a subset of regulatory T lymphocytes was identified in the patient and his unaffected mother carrying a heterozygous LRBA mutation as compared to control in a dose-dependent manner.ConclusionThis is the first description of gastric cancer and malignant melanoma in a young adult with LRBA deficiency. The role of LRBA gene knockout in cancer development and its prognosis remains to be elucidated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0682-5) contains supplementary material, which is available to authorized users.

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“…Recently, another graphical software, namely HomSI [20] has been presented, exploiting variant call format files to identify ROH with a sliding-window approach.…”

Section: Approaches For the Graphical Visualization Of Rohmentioning

confidence: 99%

Detection of Runs of Homozygosity from Whole Exome Sequencing Data: State of the Art and Perspectives for Clinical, Population and Epidemiological Studies

et al. 2014

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Runs of homozygosity (ROH) are sizeable stretches of homozygous genotypes at consecutive polymorphic DNA marker positions, traditionally captured by means of genome-wide single nucleotide polymorphism (SNP) genotyping. With the advent of next-generation sequencing (NGS) technologies, a number of methods initially devised for the analysis of SNP array data (those based on sliding-window algorithms such as PLINK or GERMLINE and graphical tools like HomozygosityMapper) or specifically conceived for NGS data have been adopted for the detection of ROH from whole exome sequencing (WES) data. In the latter group, algorithms for both graphical representation (AgileVariantMapper, HomSI) and computational detection (H³M²) of WES-derived ROH have been proposed. Here we examine these different approaches and discuss available strategies to implement ROH detection in WES analysis. Among sliding-window algorithms, PLINK appears to be well-suited for the detection of ROH, especially of the long ones. As a method specifically tailored for WES data, H³M² outperforms existing algorithms especially on short and medium ROH. We conclude that, notwithstanding the irregular distribution of exons, WES data can be used with some approximation for unbiased genome-wide analysis of ROH features, with promising applications to homozygosity mapping of disease genes, comparative analysis of populations and epidemiological studies based on consanguinity.

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HomSI: a homozygous stretch identifier from next-generation sequencing data

Abstract: HomSI software is freely available at www.igbam.bilgem.tubitak.gov.tr/softwares/HomSI, with an online manual.

Cited by 39 publications

References 13 publications

Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing

Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing

Multifocal gastric adenocarcinoma in a patient with LRBA deficiency

Detection of Runs of Homozygosity from Whole Exome Sequencing Data: State of the Art and Perspectives for Clinical, Population and Epidemiological Studies

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