Jakub Otwinowski
Associate Research ScientistCards
About
Research
Publications
2024
Learning the shape of protein microenvironments with a holographic convolutional neural network
Pun M, Ivanov A, Bellamy Q, Montague Z, LaMont C, Bradley P, Otwinowski J, Nourmohammad A. Learning the shape of protein microenvironments with a holographic convolutional neural network. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2300838121. PMID: 38300863, PMCID: PMC10861886, DOI: 10.1073/pnas.2300838121.Peer-Reviewed Original ResearchConceptsprotein structurebinding of protein complexesdesign of novel proteinsamino acid preferencesimpact of mutationsprotein functionnovel proteinsprotein complexesprotein stabilityevolutionary dataproteinphysical interactionstructure-function mappingprotein microenvironmentfunctional informationsequenceaminomutationsbindingbiologyH-CNNContrastive losses as generalized models of global epistasis
Brookes D, Otwinowski J, Sinai S. Contrastive losses as generalized models of global epistasis. 2024, 93374-93405. DOI: 10.52202/079017-2962.Peer-Reviewed Original Research
2021
Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19
Montague Z, Lv H, Otwinowski J, DeWitt W, Isacchini G, Yip G, Ng W, Tsang O, Yuan M, Liu H, Wilson I, Peiris J, Wu N, Nourmohammad A, Mok C. Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19. Cell Reports 2021, 35: 109173. PMID: 33991510, PMCID: PMC8106887, DOI: 10.1016/j.celrep.2021.109173.Peer-Reviewed Original ResearchConceptsB cell receptorSARS-CoV-2B cell response to SARS-CoV-2response to SARS-CoV-2high-throughput sequencingB cell repertoiredevelopment of rational therapiesplasma B cellssingle-cell sequencingcross-reactive responsesSARS-CoV-2 epitopesseverity of COVID-19clonal lineagesspecific to SARS-CoV-2B cellssevere acute respiratory syndrome coronavirus 2acute respiratory syndrome coronavirus 2respiratory syndrome coronavirus 2rational therapySARS-CoV-1intensive caresyndrome coronavirus 2monoclonal antibodiesmultiple time pointsdisease severity
2020
Information-Geometric Optimization with Natural Selection
Otwinowski J, LaMont C, Nourmohammad A. Information-Geometric Optimization with Natural Selection. Entropy 2020, 22: 967. PMID: 33286736, PMCID: PMC7597266, DOI: 10.3390/e22090967.Peer-Reviewed Original Researchevolutionary algorithminformation-geometric optimizationfitness landscapegradient updatesrecombination operatorevolutionary optimizationadaptive methodoptimization algorithmmatrix inversionalgorithmcomputing derivativesobjective functioncovariance matrixNewton methodoptimizationnatural selectionnatural evolutioncomputergenetics of quantitative traitsupdateoperationselectionimplementationMajor antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape
Wu N, Otwinowski J, Thompson A, Nycholat C, Nourmohammad A, Wilson I. Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape. Nature Communications 2020, 11: 1233. PMID: 32144244, PMCID: PMC7060233, DOI: 10.1038/s41467-020-15102-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ViralBinding SitesCrystallography, X-RayDNA Mutational AnalysisDogsEvolution, MolecularHEK293 CellsHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A Virus, H3N2 SubtypeMadin Darby Canine Kidney CellsMutationProtein DomainsReceptors, Cell SurfaceReverse Transcriptase Polymerase Chain ReactionRNA, ViralSequence Analysis, DNAConceptsantigenic site Blocal fitness landscapeinfluenza virushuman H3N2 influenza virusesH3N2 influenza viruseshuman H3N2 strainsinfluenza H3N2 virusinfluenza virus hemagglutininfitness landscapedeep mutational scanningH3N2 strainsH3N2 virusesantigenic driftvirus hemagglutininsite Bevolutionary constraintssequence variantsmutational scanningreceptor bindingnatural mutationsfunctional constraintsinfluenzahemagglutininantigenic spacereceptor binding modes
2019
Fierce Selection and Interference in B-Cell Repertoire Response to Chronic HIV-1
Nourmohammad A, Otwinowski J, Łuksza M, Mora T, Walczak A. Fierce Selection and Interference in B-Cell Repertoire Response to Chronic HIV-1. Molecular Biology And Evolution 2019, 36: 2184-2194. PMID: 31209469, PMCID: PMC6759071, DOI: 10.1093/molbev/msz143.Peer-Reviewed Original ResearchConceptsB cell receptoradaptive immune systemB cellsHIV-1immune responseimmune systemchronic HIV-1B cell repertoireclonal interferencehost adaptive immune systemchronic immune responseevolutionary modepopulation genetic methodschronic infectionpopulation genetic modelsCDR3 regioncoevolutionary arms racetraditional population genetic methodsclonal diversitygenetic methodsviral expansionsomatic evolutionslow down adaptationgenetic modelsrepertoire evolution
2018
Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function
Otwinowski J. Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function. Molecular Biology And Evolution 2018, 35: 2345-2354. PMID: 30085303, PMCID: PMC6188545, DOI: 10.1093/molbev/msy141.Peer-Reviewed Original ResearchInferring the shape of global epistasis
Otwinowski J, McCandlish D, Plotkin J. Inferring the shape of global epistasis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e7550-e7558. PMID: 30037990, PMCID: PMC6094095, DOI: 10.1073/pnas.1804015115.Peer-Reviewed Original Research
2016
Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections
Nourmohammad A, Otwinowski J, Plotkin J. Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections. PLOS Genetics 2016, 12: e1006171. PMID: 27442127, PMCID: PMC4956326, DOI: 10.1371/journal.pgen.1006171.Peer-Reviewed Original ResearchConceptsadaptive immune systemchronic infectionneutralizing antibodiesimmune systemHIV-infected patientsclonal lineagesrelevant to vaccine designhost-pathogen coevolutionvertebrate adaptive immune systemsignatures of coevolutionevolutionary arms raceneutralization assayantibody-antigen binding affinityvaccine designgenotype frequenciesimmune adaptationantibodieshost-pathogencoevolutionary dynamicsHIVimmune parametersviral populationsantigeninfectioncoevolution
2015
Detecting epistasis from an ensemble of adapting populations
McCandlish D, Otwinowski J, Plotkin J. Detecting epistasis from an ensemble of adapting populations. Evolution 2015, 69: 2359-2370. PMID: 26194030, PMCID: PMC5656054, DOI: 10.1111/evo.12735.Peer-Reviewed Original Research