A5089735037- Protein Structure and Dynamics
- Machine Learning in Bioinformatics
- Epigenetics and DNA Methylation
- Tryptophan and brain disorders
- Gut microbiota and health
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Cancer Research and Treatments
- Health, Environment, Cognitive Aging
- CRISPR and Genetic Engineering
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
- Metabolomics and Mass Spectrometry Studies
- Advanced biosensing and bioanalysis techniques
- DNA Repair Mechanisms
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Autophagy in Disease and Therapy
- Ginseng Biological Effects and Applications
Broad Institute
2025
McGovern Institute for Brain Research
2025
IIT@MIT
2025
Howard Hughes Medical Institute
2025
Seoul National University
2022-2024
Environmental Protection Agency
2022-2024
Northwestern University
2019-2024
Seoul National University Bundang Hospital
2022-2024
Dartmouth College
2023
University of California, Los Angeles
2018-2020
Abstract As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the query against database by describing tertiary amino acid interactions within proteins as sequences over structural alphabet. decreases computation times four to five orders magnitude with 86%, 88% and 133% sensitivities Dali, TM-align CE, respectively.
As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the query against database by describing amino acid backbone proteins as sequences over structural alphabet. decreases computation times four to five orders magnitude with 86%, 88% and 133% sensitivities DALI, TM-align CE, respectively.
Abstract Deep-learning (DL) methods like DeepMind’s AlphaFold2 (AF2) have led to substantial improvements in protein structure prediction. We analyse confident AF2 models from 21 model organisms using a new classification protocol (CATH-Assign) which exploits novel DL for structural comparison and classification. Of ~370,000 models, 92% can be assigned 3253 superfamilies our CATH domain superfamily The remaining cluster into 2367 putative superfamilies. Detailed manual analysis on 618 of...
RNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain of Cas9, we identified family DNA-targeting proteins in phage parasitic bacteria. Each system consists Tandem Interspaced Guide RNA (TIGR) array TIGR-associated (Tas) protein containing Nop domain, sometimes fused to HNH (TasH) or RuvC (TasR) nuclease domains. We show that TIGR arrays are...
Abstract Over the last year, there have been substantial improvements in protein structure prediction, particularly methods like DeepMind’s AlphaFold2 (AF2) that exploit deep learning strategies. Here we report a new CATH-Assign protocol which is used to analyse first tranche of AF2 models predicted for 21 model organisms and discuss insights these bring on nature space. We good quality those with no unusual structural characteristics, i.e., features rarely seen experimental structures. For...
Significance Pancreatic cancer is notoriously treatment resistant. These tumors rely on lysosome-dependent recycling pathways to generate substrates for metabolism, which are inhibited by chloroquine (CQ) and its derivatives. However, clinical efficacy of CQ as a monotherapy or combined with standard-of-care regimens has been limited. Using an unbiased kinome screen, we identify replication stress induced vulnerability due impaired de novo nucleotide biosynthesis find that combination...
Existing research has investigated student problem-solving strategies across science, technology, engineering, and mathematics; however, there is limited work in undergraduate biology education on how various aspects that influence learning combine to generate holistic approaches problem solving. Through the lens of situated cognition, we consider solving as a phenomenon involves interactions between internal cognition learner external environment. Using phenomenography methodology, through...
DNA methylation markers are considered robust diagnostic features in various cancer types, as epigenetic marks commonly altered during progression. Differentiation between benign prostatic hyperplasia (BPH) and early-stage prostate (PCa) is clinically difficult, relying on the information of patient's symptoms or levels prostate-specific antigen.A total 42 PCa patients 11 BPH were recruited. Genomic was purified from tissues used for library preparation target-enriched methylome with...
This study uses data from the American College of Surgeons National Quality Improvement Program databases to evaluate associations between hospital length stay and postoperative complications with readmission among patients who underwent open pancreaticoduodenectomy.
Arginine (Arg) deprivation is a promising therapeutic approach for tumors with low argininosuccinate synthetase 1 (ASS1) expression. However, its efficacy as single agent therapy needs to be improved resistance frequently observed. Methods: A tissue microarray was performed assess ASS1 expression in surgical specimens of pancreatic ductal adenocarcinoma (PDAC) and correlation disease prognosis. An RNA-Seq analysis examined the role regulating global gene transcriptome. high throughput screen...
Abstract Background Homologous recombination deficiency (HRD) stands as a clinical indicator for discerning responsive outcomes to platinum-based chemotherapy and poly ADP-ribose polymerase (PARP) inhibitors. One of the conventional approaches HRD prognostication has generally centered on identifying deleterious mutations within BRCA1/2 genes, along with quantifying genomic scars, such Genomic Instability Score (GIS) estimation scarHRD. However, scarHRD method limitations in scenarios...
Although many proteins necessitate well-folded structures to properly instigate their biological functions, a large fraction of functioning contain regions—known as intrinsically disordered protein regions—where stable are not likely form. Notable functional roles in transcriptional regulation, translation, and cellular signal transduction. Moreover, regions highly abundant associated with various human diseases, therefore these segments have become attractive drug targets for potential...
Abstract The utilization of inverse docking methods for target identification has been driven by an increasing demand efficient tools detecting potential drug side‐effects. Despite impressive achievements in the field docking, identifying true positives from a pool targets still remains challenging. Notably, most developed techniques have low accuracies, limit possible that can be investigated or are not easy to use non‐experts due lack available scripts webserver. Guided our finding...
The combination of deep learning and sequence data has transformed protein structure prediction modeling, evidenced in the success AlphaFold (AF). For this reason, many methods have been developed to take advantage areas where inaccurate structural modeling may limit computational predictiveness. example, predict intrinsic disorder from sequence, including our Rosetta ResidueDisorder (RRD) approach. Intrinsically disordered regions proteins are parts that do not form ordered, folded...
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Aim: We examined whether variation in blood-based epigenome-wide association studies could be more completely explained by augmenting existing reference DNA methylation libraries. Materials & methods: compared and enhanced libraries predicting variability three publicly available 450K datasets that collected whole-blood samples. Models were fit separately to each CpG site used estimate the additional when adjustments for cell composition made with library. Results: Calculation of mean...
Many proteins contain regions of intrinsic disorder, not folding into unique, stable conformations. Numerous experimental methods have been developed to measure the disorder all or select residues. In absence data, computational are often utilized identify these disordered and thus gain a better understanding both structure function. freely available predict from primary sequence protein, including our recently Rosetta ResidueDisorder. While very useful, they only designed sequence. However,...
ABSTRACT Overcoming the immunosuppressive tumor microenvironment is a promising strategy in anticancer therapy. L-kynurenine, strong metabolite can be degraded through kynureninases. Through homology searches and protein language models, we identified then experimentally determined efficacy of four top-ranked The catalytically most active one nearly doubles turnover number over prior best, reducing weight by 3.42 times mouse model comparisons, thus, presenting substantial therapeutic potential.
Abstract Tailor-made enzymes empower a wide range of versatile applications, although searching for the desirable often requires high throughput screening and thus poses significant challenges. In this study, we employed homology searches protein language models to discover prioritize by their kinetic parameters. We aimed kynureninases as potentially therapeutic enzyme, which hydrolyses L-kynurenine, potent immunosuppressive metabolite, overcome tumor microenvironment in anticancer therapy....
Given the diverse roles of cyclin A2 both in cell cycle regulation and DNA damage response, identifying small molecule regulators activity carries significant potential to regulate cellular processes ageing/neurodegeneration cancer.Based on A2's recently discovered role repair, we hypothesized that inhibitors were predicted bind CDK2 will be useful as a radiosensitizer cancer cells. In this study, used structure-based drug discovery find target CDK2.Molecular dynamics simulations generate...