Stephan Heijl
A5078881832- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Nutrition, Genetics, and Disease
- Genetic Associations and Epidemiology
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Molecular Biology Techniques and Applications
- RNA and protein synthesis mechanisms
Bio-Prodict (Netherlands)
2020-2023
Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks missense these genes uncertain. We analyzed data on 59,639 cases 53,165 controls from studies participating the Breast Cancer Association Consortium BRIDGES project. sampled training (80%) validation (20%) sets to analyze rare ATM (1146 variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), (472). evaluated according five silico prediction-of-deleteriousness algorithms,...
Abstract Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (CHEK2) are at an increased risk for developing breast and other cancers. While truncating CHEK2 known to be pathogenic, interpretation missense uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally clinically. Here we describe a mouse embryonic stem (mES) cell–based system quantitatively determine functional impact 50 human...
Predicting pathogenicity of missense variants in molecular diagnostics remains a challenge despite the available wealth data, such as evolutionary information, and tools to integrate that data. We describe DeepRank-Mut, configurable framework designed extract learn from physicochemically relevant features amino acids surrounding 3D space. For each variant, various atomic residue-level are extracted its structural environment, including sequence conservation scores acids, stored multi-channel...
In this white paper we introduce Helix, an AI based solution for missense pathogenicity prediction. With recent advances in the sequencing of human genomes, massive amounts genetic data have become available. This has shifted burden labor diagnostics and research from gathering to its interpretation. Helix presents a state art platform prediction variants. addition offering best-in-class predictive performance, offers that allows researchers analyze interpret variants depth can be accessed...
Abstract Despite advances in the field of missense variant effect prediction, real clinical utility current computational approaches remains rather limited. There is a large difference performance metrics reported by developers and those observed world. Most currently available predictors suffer from one or more types circularity their training evaluation strategies that lead to overestimation predictive performance. We present generic strategy independent dataset properties algorithms used,...
<div>Abstract<p>Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (<i>CHEK2)</i> are at an increased risk for developing breast and other cancers. While truncating <i>CHEK2</i> known to be pathogenic, interpretation missense uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally clinically. Here we describe a mouse embryonic stem (mES) cell–based...
Supplementary Data from Functional Analysis Identifies Damaging <i>CHEK2</i> Missense Variants Associated with Increased Cancer Risk
Supplementary Data from Functional Analysis Identifies Damaging <i>CHEK2</i> Missense Variants Associated with Increased Cancer Risk
<div>Abstract<p>Heterozygous carriers of germline loss-of-function variants in the tumor suppressor gene checkpoint kinase 2 (<i>CHEK2)</i> are at an increased risk for developing breast and other cancers. While truncating <i>CHEK2</i> known to be pathogenic, interpretation missense uncertain significance (VUS) is challenging. Consequently, many VUS remain unclassified both functionally clinically. Here we describe a mouse embryonic stem (mES) cell–based...
Abstract BACKGROUND Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2 and PALB2 are associated with increased breast cancer risk, but risks missense these genes uncertain. METHODS Combining 59,639 cases 53,165 controls, we sampled training (80%) validation (20%) sets to analyze rare ATM (1,146 variants), BRCA1 (644), BRCA2 (1,425), (325) (472). We evaluated according five in-silico prediction-of-deleteriousness algorithms, functional protein domain, frequency, using logistic regression...