A5065435409- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Medical Imaging Techniques and Applications
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Gene expression and cancer classification
- Machine Learning in Bioinformatics
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- RNA Research and Splicing
- Vector-Borne Animal Diseases
- Retinal Development and Disorders
- Genomics and Phylogenetic Studies
- Animal Genetics and Reproduction
- Gene Regulatory Network Analysis
- Enzyme Structure and Function
- Neural Networks and Applications
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Asthma and respiratory diseases
University of British Columbia
2015-2024
British Columbia Children's Hospital
2017-2024
Universitat Pompeu Fabra
2008-2021
Child and Family Research Institute
2016
Municipal Institute for Medical Research
2009
Barcelona Biomedical Research Park
2009
QB3
2009
Centro de Investigacion Principe Felipe
2009
Abstract JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release JASPAR, the CORE collection has been expanded with 245 new PFMs (169 vertebrates, 42 plants, 17 nematodes, 10 insects, and 7 fungi), 156 were updated (125 28 plants 3 insects). These represent 18% expansion compared to previous...
Abstract JASPAR (http://jaspar.genereg.net/) is an open-access database containing manually curated, non-redundant transcription factor (TF) binding profiles for TFs across six taxonomic groups. In this 9th release, we expanded the CORE collection with 341 new (148 plants, 101 vertebrates, 85 urochordates, and 7 insects), which corresponds to a 19% expansion over previous release. We added 298 Unvalidated when no orthogonal evidence was found in literature. All were clustered provide...
JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six taxonomic groups. In the 2018 release JASPAR, CORE collection has been expanded with 322 new PFMs (60 vertebrates 262 plants) 33 were updated (24 vertebrates, 8 plants 1 insects). These represent a 30% expansion compared to 2016 release. addition, we...
JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the CORE collection with 494 new TF (315 vertebrates, 11 nematodes, 3 insects, 1 fungi and 164 plants) updated 59 (58 vertebrates fungi). The introduced represent 83% expansion 10% update when compared to previous release....
JASPAR (https://jaspar.elixir.no/) is a widely-used open-access database presenting manually curated high-quality and non-redundant DNA-binding profiles for transcription factors (TFs) across taxa. In this 10th release 20th-anniversary update, the CORE collection has expanded with 329 new profiles. We updated three existing provided orthogonal support 72 from previous release's UNVALIDATED collection. Altogether, 2024 update provides 20% increase in release. A trimming algorithm enhanced by...
STAT6 (signal transducer and activator of transcription 6) is a factor that plays central role in the pathophysiology allergic inflammation. We have identified 16 patients from 10 families spanning three continents with profound phenotype early-life onset immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, anaphylaxis. The cases were either sporadic (seven...
Interferon regulatory factor 4 (IRF4) is a transcription (TF) and key regulator of immune cell development function. We report recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) seven patients from six unrelated families. The exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii , presented with agammaglobulinemia. Patients’ B cells showed impaired maturation, decreased immunoglobulin isotype...
Deep learning models such as convolutional neural networks (CNNs) excel in genomic tasks but lack interpretability. We introduce ExplaiNN, which combines the expressiveness of CNNs with interpretability linear models. ExplaiNN can predict TF binding, chromatin accessibility, and de novo motifs, achieving performance comparable to state-of-the-art methods. Its predictions are transparent, providing global (cell state level) well local (individual sequence biological insights into data. serve...
Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment the utility SNP data for predicting efficacy RA patients was performed context a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled comparative evaluation predictions developed by...
Abstract Background Positional weight matrix (PWM) is a de facto standard model to describe transcription factor (TF) DNA binding specificities. PWMs inferred from in vivo or vitro data are stored many databases and used plethora of biological applications. This calls for comprehensive benchmarking public PWM models with large experimental reference sets. Results Here we report results all-against-all sites human TFs on compilation (HT-SELEX, PBM) (ChIP-seq) data. We observe that the best...
The complementarity of gene expression and protein-DNA interaction data led to several successful models biological systems.However, recent studies in multiple species raise doubts about the relationship between these two datasets.These show that overwhelming majority genes bound by a particular transcription factor (TF) are not affected when is knocked out.Here, we this surprising result can be partially explained considering broader cellular context which TFs operate.Factors whose...
Abstract Background X-chromosome inactivation (XCI) in eutherian mammals is the epigenetic of one two X chromosomes XX females order to compensate for dosage differences with XY males. Not all genes are inactivated, and proportion escaping from varies between human mouse (the species that have been extensively studied). Results We used DNA methylation predict XCI status X-linked CpG islands across 12 different species: human, chimp, bonobo, gorilla, orangutan, mouse, cow, sheep, goat, pig,...
Abstract Background Deep learning has proven to be a powerful technique for transcription factor (TF) binding prediction but requires large training datasets. Transfer can reduce the amount of data required deep learning, while improving overall model performance, compared separate each new task. Results We assess transfer strategy TF consisting pre-training step, wherein we train multi-task with multiple TFs, and fine-tuning initialize single-task models individual TFs weights learned by...
Diseases and phenotypes caused by disrupted transcription factor (TF) binding are being identified, but progress is hampered our limited capacity to predict such functional alterations. Improving predictions may be dependent on expanding the set of bona fide TF Allele-specific (ASB) events, where TFs preferentially bind one two alleles at heterozygous sites, reveal impact sequence variations in altered binding. Here, we present largest ASB compilation knowledge, 10 765 events retrieved from...
MiniPromoters, or compact promoters, are short DNA sequences that can drive expression in specific cells and tissues. While broadly useful, they of high relevance to gene therapy due their role enabling precise control where a therapeutic will be expressed. Here, we present OnTarget (http://ontarget.cmmt.ubc.ca), webserver streamlines the MiniPromoter design process. Users only need specify interest custom genomic coordinates on which focus identification promoters enhancers, also provide...
SUMMARY We describe an effort (“Codebook”) to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well 61 control TFs. Nearly 5,000 independent experiments across multiple in vitro vivo assays produced motifs for just over half TFs analyzed (177, or 53%), which most are unique a single TF. The data highlight extensive contribution transposable elements TF evolution, both cis trans , identify tens thousands conserved, base-level...
Small and cell-type restricted promoters are important tools for basic preclinical research, clinical delivery of gene therapies. In therapy, ophthalmic trials have been leading the field, with over 50% ocular using that restrict expression based on cell type. Here, 19 human DNA MiniPromoters were bioinformatically designed rAAV, tested by neonatal intravenous in mouse, successful went to be intravitreal, subretinal, intrastromal, and/or adult mouse. We present promoter development as an...
Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors known processes involved endoderm (mTOR, PI3K, and JNK pathways) new compound, with an unknown mechanism action, capable inducing absence growth factors media. Optimization classical protocol by inclusion this compound...
Retinal gene therapy is leading the neurological field, with 32 ongoing clinical trials of recombinant adeno-associated virus (rAAV)-based therapies. Importantly, over 50% those are using restricted promoters from human genes. Promoters that restrict expression have demonstrated increased efficacy and can limit therapeutic to target cells thereby reducing unwanted off-target effects. ganglion a critical in ocular therapy; they involved common diseases such as glaucoma, rare Leber's...
Leishmania species are intracellular protozoan pathogens that have evolved to successfully infect and deactivate host macrophages. How this deactivation is brought about not completely understood. Recently, microRNAs (miRNAs) emerged as ubiquitous regulators of macrophage gene expression contribute shaping the immune responses pathogens. Conversely, several ability exploit miRNA manipulate host-cell phenotype. However, very little known mechanisms used by drive changes in abundance. Using...
Abstract Disease-causing mutations in genes encoding transcription factors (TFs) can affect TF interactions with their cognate DNA-binding motifs. Whether and how impact upon the binding to composite elements (CE) interaction other TFs is unclear. Here, we report a distinct mechanism of alteration human lymphomas perturbed B cell identity, particular classic Hodgkin lymphoma. It caused by recurrent somatic missense mutation c.295 T > C (p.Cys99Arg; p.C99R) targeting center domain...