Discovery of structural deletions in breast cancer predisposition genes using whole genome sequencing data from > 2000 women of African-ancestry

2021 ◽  
Author(s):  
Zhishan Chen ◽  
Xingyi Guo ◽  
Jirong Long ◽  
Jie Ping ◽  
Bingshan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
African Ancestry ◽  
Cancer Predisposition ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Breast Cancer Predisposition ◽  
Predisposition Genes

scholarly journals Validation of HER2 status in whole genome sequencing data of breast cancers with AI-driven, ploidy-corrected approach

2021 ◽  
Author(s):  
Marzena Wojtaszewska ◽  
Rafal Stepien ◽  
Alicja Wozna ◽  
Maciej Piernik ◽  
Maciej Dabrowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cancer Diagnostics ◽  
Her2 Status ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Sequencing Data ◽  
Genomic Context

The HER2 protein overexpression is one of the most significant biomarkers for breast cancer diagnostics, prediction, and prognostics. The availability of HER2-inhibitors in routine clinical practice directly translates into a diagnostic need for precise and robust marker identification. At the brink of the genomic era, multigene next-generation sequencing methodologies slowly take over the field of single-biomarker molecular and cytogenetic tests. However, copy number alterations such as amplification of the HER2-coding ERBB2 gene, are certainly harder to validate as an NGS biomarker than simple SNV mutations. They are characterized by several compound genomic factors i.a. structural heterogeneity, dependence on chromosome count and genomic context of ploidy. In our study, we tested the approach of using whole genome sequencing instead of NGS panels to robustly and accurately determine HER2 status in clinical setup. Based on the large dataset of 877 breast cancer patients' genomes with curated clinical data and a machine learning approach for optimization of an unbiased diagnostic classifier, we provide a reliable algorithm of HER2 status assessment.

scholarly journals A population-specific reference panel for improved genotype imputation in African Americans

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jared O’Connell ◽  
Taedong Yun ◽  
Meghan Moreno ◽  
Helen Li ◽  
Nadia Litterman ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
African Ancestry ◽  
Genotype Imputation ◽  
Whole Genome Sequencing Data ◽  
Specific Reference ◽  
Whole Genome ◽  
Sequencing Data ◽  
High Quality ◽  
Sub Saharan

AbstractThere is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals. With the exception of the TOPMed imputation server (which notably cannot be downloaded), our panel substantially outperformed other available panels when imputing African American individuals. The raw sequencing data, variant calls and imputation panel for this cohort are all freely available via dbGaP and should prove an invaluable resource for further study of admixed African genetics.

scholarly journals Integrative reconstruction of cancer genome karyotypes using InfoGenomeR

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yeonghun Lee ◽  
Hyunju Lee
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Glioblastoma Multiforme ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Metastatic Cancer ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
A Genome

AbstractAnnotation of structural variations (SVs) and base-level karyotyping in cancer cells remains challenging. Here, we present Integrative Framework for Genome Reconstruction (InfoGenomeR)-a graph-based framework that can reconstruct individual SVs into karyotypes based on whole-genome sequencing data, by integrating SVs, total copy number alterations, allele-specific copy numbers, and haplotype information. Using whole-genome sequencing data sets of patients with breast cancer, glioblastoma multiforme, and ovarian cancer, we demonstrate the analytical potential of InfoGenomeR. We identify recurrent derivative chromosomes derived from chromosomes 11 and 17 in breast cancer samples, with homogeneously staining regions for CCND1 and ERBB2, and double minutes and breakage-fusion-bridge cycles in glioblastoma multiforme and ovarian cancer samples, respectively. Moreover, we show that InfoGenomeR can discriminate private and shared SVs between primary and metastatic cancer sites that could contribute to tumour evolution. These findings indicate that InfoGenomeR can guide targeted therapies by unravelling cancer-specific SVs on a genome-wide scale.

scholarly journals Whole genome sequencing reveals high differentiation, low levels of genetic diversity and short runs of homozygosity among Swedish wels catfish

Heredity ◽  
2021 ◽  
Author(s):  
Axel Jensen ◽  
Mette Lillie ◽  
Kristofer Bergström ◽  
Per Larsson ◽  
Jacob Höglund
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome Sequencing Data ◽  
Peripheral Populations ◽  
Whole Genome ◽  
Runs Of Homozygosity ◽  
Sequencing Data ◽  
Isolated Populations ◽  
Native Populations

AbstractThe use of genetic markers in the context of conservation is largely being outcompeted by whole-genome data. Comparative studies between the two are sparse, and the knowledge about potential effects of this methodology shift is limited. Here, we used whole-genome sequencing data to assess the genetic status of peripheral populations of the wels catfish (Silurus glanis), and discuss the results in light of a recent microsatellite study of the same populations. The Swedish populations of the wels catfish have suffered from severe declines during the last centuries and persists in only a few isolated water systems. Fragmented populations generally are at greater risk of extinction, for example due to loss of genetic diversity, and may thus require conservation actions. We sequenced individuals from the three remaining native populations (Båven, Emån, and Möckeln) and one reintroduced population of admixed origin (Helge å), and found that genetic diversity was highest in Emån but low overall, with strong differentiation among the populations. No signature of recent inbreeding was found, but a considerable number of short runs of homozygosity were present in all populations, likely linked to historically small population sizes and bottleneck events. Genetic substructure within any of the native populations was at best weak. Individuals from the admixed population Helge å shared most genetic ancestry with the Båven population (72%). Our results are largely in agreement with the microsatellite study, and stresses the need to protect these isolated populations at the northern edge of the distribution of the species.

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