A5078827216- Bioinformatics and Genomic Networks
- Protein Kinase Regulation and GTPase Signaling
- 14-3-3 protein interactions
- Computational Drug Discovery Methods
- Microtubule and mitosis dynamics
- Machine Learning in Bioinformatics
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Explainable Artificial Intelligence (XAI)
- Advanced Graph Neural Networks
- Melanoma and MAPK Pathways
- Gene expression and cancer classification
- PI3K/AKT/mTOR signaling in cancer
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cell Image Analysis Techniques
- Mass Spectrometry Techniques and Applications
University of Georgia
2021-2024
University of Liverpool
2023
The human genome encodes over 500 distinct protein kinases which regulate nearly all cellular processes by the specific phosphorylation of substrates. While advances in mass spectrometry and proteomics studies have identified thousands sites across species, information on that phosphorylate these is currently lacking for vast majority phosphosites. Recently, there has been a major focus development computational models predicting kinase-substrate associations. However, most current only...
The ion channel (IC) genes encoded in the human genome play fundamental roles cellular functions and disease are one of largest classes druggable proteins. However, limited knowledge diverse molecular carried out by ICs presents a major bottleneck developing selective chemical probes for modulating their states. wealth sequence data available on from organisms provides valuable source untapped information illuminating unique modes regulation functional specialization. extensive...
Protein language models, trained on millions of biologically observed sequences, generate feature-rich numerical representations protein sequences. These representations, called sequence embeddings, can infer structure-functional properties, despite models being primary alone. While embeddings have been applied toward tasks such as structure and function prediction, applications alignment-free classification hindered by the lack studies to derive, quantify evaluate relationships between...
Protein kinases are among the largest druggable family of signaling proteins, involved in various human diseases, including cancers and neurodegenerative disorders. Despite their clinical relevance, nearly 30% 545 protein remain highly understudied. Comparative genomics is a powerful approach for predicting investigating functions understudied kinases. However, an incomplete knowledge kinase orthologs across fully sequenced kinomes severely limits application comparative approaches...
Abstract Motivation Phosphorylation, a post-translational modification regulated by protein kinase enzymes, plays an essential role in almost all cellular processes. Understanding how each of the nearly 500 human kinases selectively phosphorylates their substrates is foundational challenge bioinformatics and cell signaling. Although deep learning models have been popular means to predict kinase–substrate relationships, existing often lack interpretability are trained on datasets skewed...
Catalytic signaling outputs of protein kinases are dynamically regulated by an array structural mechanisms, including allosteric interactions mediated intrinsically disordered segments flanking the conserved catalytic domain. The doublecortin-like (DCLKs) a family microtubule-associated proteins characterized flexible C-terminal autoregulatory 'tail' segment that varies in length across various human DCLK isoforms. However, mechanism whereby these isoform-specific variations contribute to...
The Protein Kinase Ontology (ProKinO) is an integrated knowledge graph that conceptualizes the complex relationships among protein kinase sequence, structure, function, and disease in a human machine-readable format. In this study, we have significantly expanded ProKinO by incorporating additional data on expression patterns drug interactions. Furthermore, developed completely new browser from ground up to render visible interactive web. We enriched with classes capture information ligand...
Hydrophobic cores are fundamental structural properties of proteins typically associated with protein folding and stability; however, how the hydrophobic core shapes evolution function is poorly understood. Here, we investigated role conserved in fold-A glycosyltransferases (GT-As), a large superfamily enzymes that catalyze formation glycosidic linkages between diverse donor acceptor substrates through distinct catalytic mechanisms (inverting versus retaining). Using hidden Markov models...
ABSTRACT The Protein Kinase Ontology (ProKinO) is an integrated knowledge graph that conceptualizes the complex relationships connecting protein kinase sequence, structure, function, and disease in a human machine-readable format. Here we extend scope of ProKinO as discovery tool by including new classes capturing information on ligand binding sites, expression patterns, functional features, demonstrate its application uncovering regarding understudied members family. Specifically, through...
The 534 protein kinases encoded in the human genome constitute a large druggable class of proteins that include both well-studied and understudied "dark" members. Accurate prediction dark kinase functions is major bioinformatics challenge. Here, we employ graph mining approach uses evolutionary functional context knowledge graphs (KGs) to predict pathway associations for kinases. We propose new scalable embedding approach, RegPattern2Vec, which employs regular pattern constrained random...
The Ca2+-independent, but diacylglycerol-regulated, novel protein kinase C (PKC) theta (θ) is highly expressed in hematopoietic cells where it participates immune signaling and platelet function. Mounting evidence suggests that PKCθ may be involved cancer, particularly blood cancers, breast gastrointestinal stromal tumors, yet how to target this (as an oncogene or as a tumor suppressor) has not been established. Here, we examine the effect of four cancer-associated mutations, R145H/C...
Catalytic signaling outputs of protein kinases are dynamically regulated by an array structural mechanisms, including allosteric interactions mediated intrinsically disordered segments flanking the conserved catalytic domain. The Doublecortin Like Kinases (DCLKs) a family microtubule-associated proteins characterized flexible C-terminal autoregulatory 'tail' segment that varies in length across various human DCLK isoforms. However, mechanism whereby these isoform-specific variations...
Catalytic signaling outputs of protein kinases are dynamically regulated by an array structural mechanisms, including allosteric interactions mediated intrinsically disordered segments flanking the conserved catalytic domain. The Doublecortin Like Kinases (DCLKs) a family microtubule-associated proteins characterized flexible C-terminal autoregulatory ‘tail’ segment that varies in length across various human DCLK isoforms. However, mechanism whereby these isoform-specific variations...
Abstract Protein kinases are among the largest druggable family of signaling proteins, involved in various human diseases, including cancers and neurodegenerative disorders. Despite their clinical relevance, nearly 30% 545 protein remain highly understudied. Comparative genomics is a powerful approach for predicting investigating functions understudied kinases. However, an incomplete knowledge kinase orthologs across fully sequenced kinomes severely limits application comparative approaches...
ABSTRACT Protein classification is a cornerstone of biology that relies heavily on alignment-based comparison primary sequences. However, the systematic large protein superfamilies impeded by unique challenges in aligning divergent sequence datasets. We developed an alignment-free approach for analysis and using embedding vectors generated from pre-trained language models capture underlying structural-functional properties unsupervised training millions biologically-observed constructed...
Catalytic signaling outputs of protein kinases are dynamically regulated by an array structural mechanisms, including allosteric interactions mediated intrinsically disordered segments flanking the conserved catalytic domain. The Doublecortin Like Kinases (DCLKs) a family microtubule-associated proteins characterized flexible C-terminal autoregulatory ‘tail’ segment that varies in length across various human DCLK isoforms. However, mechanism whereby these isoform-specific variations...
Catalytic signaling outputs of protein kinases are dynamically regulated by an array structural mechanisms, including allosteric interactions mediated intrinsically disordered segments flanking the conserved catalytic domain. The doublecortin-like (DCLKs) a family microtubule-associated proteins characterized flexible C-terminal autoregulatory ‘tail’ segment that varies in length across various human DCLK isoforms. However, mechanism whereby these isoform-specific variations contribute to...