is a software tool that scans genetic variants against position weight matrices of transcription factors (TF) to determine the potential for the disruption of TF binding at the site of the variant. It leverages the Bioconductor suite of software packages and annotations to operate across a diverse array of genomes and motif databases. Initially developed to interrogate the effect of single nucleotide variants (common and rare SNVs) on potential TF binding sites, in v2, we have updated the functionality. New features include the ability to query other types of more complex genetic variants, such as short insertions and deletions (indels). This function allows modeling a more extensive array of variants that may have more significant effects on TF binding. Additionally, while TF binding is based partly on sequence preference, predictions of TF binding based on sequence preference alone can indicate many more potential binding events than observed. Adding information from DNA-binding sequencing datasets lends confidence to motif disruption prediction by demonstrating TF binding in cell lines and tissue types. Therefore, implements querying the ReMap2022 database for evidence that a TF matching the disrupted motif binds over the disrupting variant. Finally, in , in addition to the existing interface, we have implemented an R/Shiny graphical user interface to simplify and enhance access to researchers with different skill sets.
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J Assist Reprod Genet
January 2025
Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research Group Genetics, Reproduction and Development, Centre for Medical Genetics, Laarbeeklaan 101, 1090, Brussels, Belgium.
Purpose: Primary ovarian insufficiency (POI) is an important cause of female infertility, stemming from follicle dysfunction or premature oocyte depletion. Pathogenic variants in genes such as NOBOX, GDF9, BMP15, and FSHR have been linked to POI. NOBOX, a transcription factor expressed in oocytes and granulosa cells, plays a pivotal role in folliculogenesis.
View Article and Find Full Text PDFEur J Hum Genet
January 2025
CENTOGENE GmbH, Rostock, Germany.
We aimed to assess the impact of splicing variants reported in our laboratory to gain insight into their clinical relevance. A total of 108 consecutive individuals, for whom 113 splicing variants had been reported, were selected for RNA-sequencing (RNA-seq), considering the gene expression in blood. A protocol was developed to perform RNA extraction and sequencing using the same sample (dried blood spots, DBS) provided for the DNA analysis, including library preparation and bioinformatic pipeline analysis.
View Article and Find Full Text PDFEur J Hum Genet
January 2025
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
The etiology of congenital heart disease (CHD) is complex, comprising both genetic and environmental factors. Despite documented familial occurrences, the genetic etiology remains largely elusive. Trio exome sequencing identified a heterozygous FLT4 splice site variant in two families with respectively tetralogy of Fallot (TOF), and variable CHD comprising both the TOF spectrum and aortic coarctation.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
CRCL, Centre Léon Bérard, Lyon, France.
Publicly available trial matching tools can improve the access to therapeutic innovations, but errors may expose to over-solicitation and disappointment. We performed a pragmatic non-interventional prospective evaluation on sequential patients at the Molecular Tumor Board of Centre Leon Berard. During 10 weeks in 2024, we analysed 157 patients with four clinical trial matching tools from the 19 screened: Klineo, ScreenAct, Trialing and DigitalECMT.
View Article and Find Full Text PDFSci Rep
January 2025
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #04-06 Immunos, Singapore, 138648, Singapore.
The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution.
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