Constantina Bakolitsa
A5008667207- Enzyme Structure and Function
- Genomics and Rare Diseases
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Biomedical Text Mining and Ontologies
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- Genomic variations and chromosomal abnormalities
- Biochemical and Molecular Research
- Genetic factors in colorectal cancer
- Bioinformatics and Genomic Networks
- Microtubule and mitosis dynamics
- Machine Learning in Bioinformatics
- RNA modifications and cancer
- Lysosomal Storage Disorders Research
- Microbial Natural Products and Biosynthesis
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Genetics and Neurodevelopmental Disorders
- Force Microscopy Techniques and Applications
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
University of California, Berkeley
2019-2025
Sanford Burnham Prebys Medical Discovery Institute
2004-2013
Joint Center for Structural Genomics
2009-2010
University of California, San Diego
2010
Salk Institute for Biological Studies
2010
Discovery Institute
2009
Institute for Medical Research
2009
University of Leicester
1999
Abstract Critical evaluation of computational tools for predicting variant effects is important considering their increased use in disease diagnosis and driving molecular discoveries. In the sixth edition Assessment Genome Interpretation (CAGI) challenge, a dataset 28 STK11 rare variants (27 missense, 1 single amino acid deletion), identified primary non-small cell lung cancer biopsies, was experimentally assayed to characterize methods from four participating teams five publicly available...
Determination of first protein structures, from hundreds families unknown function, have shown that divergence, rather than novelty, is the dominant force shapes evolution universe.
Abstract Regular, systematic, and independent assessment of computational tools used to predict the pathogenicity missense variants is necessary evaluate their clinical research utility suggest directions for future improvement. Here, as part sixth edition Critical Assessment Genome Interpretation (CAGI) challenge, we assess variant effect predictors (or impact predictors) on an evaluation dataset rare from disease-relevant databases. Our evaluates submitted CAGI6 Annotate-All-Missense...
Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict variant's impact on needed interpret the growing number variants unknown significance (VUS) identified by exome genome sequencing. Here, we present results CAGI6 Splicing VUS challenge, invited predictions 56 ascertained clinically functionally validated determine impact. The performance 12 prediction methods, along with SpliceAI CADD,...
Retinal ganglion cells exhibit substantial correlated firing: a tendency to fire nearly synchronously at rates different from those expected by chance. These correlations suggest that network interactions significantly shape the visual signal transmitted eye brain. This study describes degree and structure of firing among major cell types in primate retina. Correlated ON OFF parasol, midget, small bistratified cells, which together constitute roughly 75% input higher areas, was studied using...
Abstract Background A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing genome-wide. To aid the interpretation prioritization of vast number detected, computational methods proliferating. Knowing which tools most effective remains unclear. evaluate performance methods, to encourage innovation method development, we designed Critical...
Abstract Regular, systematic, and independent assessments of computational tools that are used to predict the pathogenicity missense variants necessary evaluate their clinical research utility guide future improvements. The Critical Assessment Genome Interpretation (CAGI) conducts ongoing Annotate-All-Missense (Missense Marathon) challenge, in which variant effect predictors (also called impact predictors) evaluated on added disease-relevant databases following prediction submission...
Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC subtilis have both previously been characterized as highly specific γ-d-glutamyl-l-diamino acid endopeptidases. The crystal structure of a ortholog cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain is ubiquitous very large family cell-wall-related cysteine peptidases. A bound reaction product (l-Ala-γ-d-Glu) enabled...
Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods accurately determine clinical impact variants unknown significance (VUS). Towards this goal, ARSA Critical Assessment Genome Interpretation (CAGI) challenge was designed characterize progress by utilizing 219 experimentally assayed missense VUS
Pleckstrin homology (PH) domains have been identified only in eukaryotic proteins to date. We determined crystal structures for three members of an uncharacterized protein family (Pfam PF08000), which provide compelling evidence the existence PH-like bacteria (PHb). The first two contain a single PHb domain that forms dome-shaped, oligomeric ring with C(5) symmetry. third structure has additional helical hairpin attached at C-terminus and similar but much larger C(12) Thus, both molecular...
Membrane-attack complex/perforin (MACPF) proteins are transmembrane pore-forming that important in both human immunity and the virulence of pathogens. Bacterial MACPFs found diverse bacterial species, including most gut-associated Bacteroides species. The crystal structure a MACPF-domain-containing protein BT_3439 (Bth-MACPF) from B. thetaiotaomicron, predominant member mammalian intestinal microbiota, has been determined. Bth-MACPF contains membrane-attack domain two novel C-terminal...
The NIH Protein Structure Initiative centers, such as the Joint Center for Structural Genomics (JCSG), have developed highly efficient technological platforms that are capable of experimentally determining three-dimensional structures hundreds proteins per year. However, overwhelming majority almost 5000 protein determined by these centers yet to be described in peer-reviewed literature. In a high-throughput structural genomics environment, process structure determination occurs...
A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. Rare Genomes Project (RGP) direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis gene discovery. Families consented sharing sequence phenotype data with researchers, allowing development Critical Assessment Genome Interpretation (CAGI) community challenge, placing...
SsgA-like proteins (SALPs) are a family of homologous cell division-related that occur exclusively in morphologically complex actinomycetes. We show SsgB, subfamily SALPs, is the archetypal SALP functionally conserved all sporulating Sporulation-specific division Streptomyces coelicolor ssgB mutants restored by introduction distant orthologues from other Interestingly, number septa (and spores) complemented null dictated specific orthologue expressed. The crystal structure SsgB Thermobifida...
The NAGLU challenge of the fourth edition Critical Assessment Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict impact variants unknown significance (VUS) on enzymatic activity lysosomal hydrolase α-N-acetylglucosaminidase (NAGLU). Deficiencies lead a rare, monogenic, recessive storage disorder, Sanfilippo syndrome type B (MPS IIIB). This attracted 17 submissions from 10 groups. We observed that top models were able missense mutations with Pearson's...
The first structural representative of the domain unknown function DUF2006 family, also known as Pfam family PF09410, comprises a lipocalin-like fold with duplication. finding calycin signature in N-terminal domain, combined remote sequence similarity to two other protein families (PF07143 and PF08622) implicated isoprenoid metabolism oxidative stress response, support an involvement lipid metabolism. Clusters conserved residues that interact ligand mimetics suggest binding regulation sites...
Abstract Background Many protein structures determined in high-throughput structural genomics centers, despite their significant novelty and importance, are available only as PDB depositions not accompanied by a peer-reviewed manuscript. Because of this they accessible the standard tools literature searches, remaining underutilized broad biological community. Results To address issue we have developed TOPSAN, The Open Protein Structure Annotation Network, web-based platform that combines...
The Open Protein Structure Annotation Network (TOPSAN) is a web-based collaboration platform for exploring and annotating structures determined by structural genomics efforts. Characterization of those presents challenge since the majority proteins themselves have not yet been characterized. Responding to this challenge, TOPSAN facilitates collaborative annotation investigation via user-friendly interface pre-populated with automatically generated information. Semantic web technologies...
SSO2064 is the first structural representative of PF01796 (DUF35), a large prokaryotic family with wide phylogenetic distribution. The structure reveals novel two-domain architecture comprising an N-terminal, rubredoxin-like, zinc ribbon and C-terminal, oligonucleotide/oligosaccharide-binding (OB) fold domain. Additional N-terminal helical segments may be involved in protein-protein interactions. Domain architectures, genomic context analysis functional evidence from certain bacterial...