Jochen Weile
YOU?
Author Swipe
View article: Systematic and proactive evaluation of AIRE missense variant effects
Systematic and proactive evaluation of AIRE missense variant effects Open
Pathogenic variants in the Autoimmune Regulator (AIRE) gene cause Autoimmune Polyendocrine Syndrome Type 1 (APS-1), a rare primary immunodeficiency disease with symptoms including hypoparathyroidism, adrenal insufficiency, and chronic muco…
View article: The functional landscape of coding variation in the familial hypercholesterolemia gene <i>LDLR</i>
The functional landscape of coding variation in the familial hypercholesterolemia gene <i>LDLR</i> Open
Variants in the familial hypercholesterolemia gene LDLR —the most important genetic driver of cardiovascular disease—can raise circulating low-density lipoprotein (LDL) cholesterol concentrations and increase the risk of premature atherosc…
LLM-based data extraction for a large cancer registry, the Ontario Hereditary Cancer Research Network Open
Importance Manual data extraction from genomic lab reports for on-line registries and databases is time-consuming for human resources such as clinical research coordinators. Automated tools, especially LLMs, can address these issues. Effic…
View article: Comprehensively Testing the Function of Missense Variation in the <i>STK11</i> Tumour Suppressor
Comprehensively Testing the Function of Missense Variation in the <i>STK11</i> Tumour Suppressor Open
The tumor suppressor gene STK11 encoding Serine/Threonine Kinase 11 (STK11) is associated with Peutz-Jeghers Syndrome (PJS), a heritable gastrointestinal disease that increases lifetime cancer risk, and with somatic variation that contribu…
View article: Landscapes of missense variant impact for human superoxide dismutase 1
Landscapes of missense variant impact for human superoxide dismutase 1 Open
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease for which important subtypes are caused by variation in the Superoxide Dismutase 1 gene SOD1 . Diagnosis based on SOD1 sequencing can not only be definitive but also…
View article: Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve <i>KCNH2</i> -LQTS Variant Classification and Cardiac Event Risk Stratification
Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve <i>KCNH2</i> -LQTS Variant Classification and Cardiac Event Risk Stratification Open
BACKGROUND: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2 . Variant classification is difficult, often because of lack of functional data. Mo…
View article: Pacybara: accurate long-read sequencing for barcoded mutagenized allelic libraries
Pacybara: accurate long-read sequencing for barcoded mutagenized allelic libraries Open
Motivation Long-read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some applications, e.g. sequencing mutagen…
A missense variant effect map for the human tumour suppressor protein CHK2 Open
The tumour suppressor CHEK2 encodes the serine/threonine protein kinase CHK2 which, upon DNA damage, is important for pausing the cell cycle, initiating DNA repair and inducing apoptosis. CHK2 phosphorylation of the tumour suppressor BRCA1…
View article: Multiplexed Assays of Variant Effect and Automated Patch-clamping Improve<i>KCNH2</i>-LQTS Variant Classification and Cardiac Event Risk Stratification
Multiplexed Assays of Variant Effect and Automated Patch-clamping Improve<i>KCNH2</i>-LQTS Variant Classification and Cardiac Event Risk Stratification Open
Background Long QT syndrome (LQTS) is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2 . Variant classification is difficult, often owing to lack of functional data…
View article: Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR/Cas9 screens
Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR/Cas9 screens Open
Zhao et al. performed phenotypic CRISPR screens to uncover genes and pathways that suppress DNA damage in human cells.
View article: Pacybara: Accurate long-read sequencing for barcoded mutagenized allelic libraries
Pacybara: Accurate long-read sequencing for barcoded mutagenized allelic libraries Open
Summary Long read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some applications, e.g. sequencing mutagenize…
Proactive Variant Effect Mapping to Accelerate Genetic Diagnosis for Pediatric Cardiac Arrest Open
While genetic testing is becoming mainstream in the management of patients with potentially inherited cardiovascular disease, the prevalence of uncertain results severely limits its utility. One promising approach is to generate variant ef…
Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation Open
Defects in hydroxymethylbilane synthase (HMBS) can cause Acute Intermittent Porphyria (AIP), an acute neurological disease. Although sequencing-based diagnosis can be definitive, ~⅓ of clinical HMBS variants are missense variants, and most…
View article: Additional file 2 of A comprehensive map of human glucokinase variant activity
Additional file 2 of A comprehensive map of human glucokinase variant activity Open
Additional file 2.
View article: Genome-scale mapping of DNA damage suppressors identifies GNB1L as essential for ATM and ATR biogenesis
Genome-scale mapping of DNA damage suppressors identifies GNB1L as essential for ATM and ATR biogenesis Open
To maintain genome integrity, cells must avoid DNA damage by ensuring the accurate duplication of the genome and by having efficient repair and signaling systems that counteract the genome-destabilizing potential of DNA lesions. To uncover…
Proactive Variant Effect Mapping to Accelerate Genetic Diagnosis for Pediatric Cardiac Arrest Open
While genetic testing is becoming standard of care for patients with potentially inherited cardiovascular disease, the prevalence of uncertain results severely limits its utility. One promising approach is to generate variant effect maps t…
Improved pathogenicity prediction for rare human missense variants Open
(The American Journal of Human Genetics 108, 1891–1906; October 7, 2021) In the originally published version of this article, Hanqing Liu was omitted from the author list. The author list has now been corrected online and includes Hanqing …
A systematic genotype-phenotype map for missense variants in the human intellectual disability-associated gene<i>GDI1</i> Open
Next generation sequencing has become a common tool in the diagnosis of genetic diseases. However, for the vast majority of genetic variants that are discovered, a clinical interpretation is not available. Variant effect mapping allows the…
Improved pathogenicity prediction for rare human missense variants Open
The success of personalized genomic medicine depends on our ability to assess the pathogenicity of rare human variants, including the important class of missense variation. There are many challenges in training accurate computational syste…
Empowering rare variant burden-based gene-trait association studies via optimized computational predictor choice Open
Background Causal gene/trait relationships can be identified via observation of an excess (or reduced) burden of rare variation in a given gene within humans who have that trait. Although computational predictors can improve the power of s…
MaveRegistry: a collaboration platform for multiplexed assays of variant effect Open
Summary Multiplexed assays of variant effect (MAVEs) are capable of experimentally testing all possible single nucleotide or amino acid variants in selected genomic regions, generating ‘variant effect maps’, which provide biochemical insig…
Prioritizing genes for systematic variant effect mapping Open
Motivation When rare missense variants are clinically interpreted as to their pathogenicity, most are classified as variants of uncertain significance (VUS). Although functional assays can provide strong evidence for variant classification…
MaveRegistry: a collaboration platform for multiplexed assays of variant effect Open
Summary Multiplexed assays of variant effect (MAVEs) are capable of experimentally testing all possible single nucleotide or amino acid variants in selected genomic regions, generating ‘variant effect maps’, which provide biochemical insig…