Mostlaboratoriesstudyingbiologicalprocessesandhumandiseaseusemicroscopestoimagesamples. Whetherinsmallorlargescalemicroscopyexperiments,biologistsincreasinglyneedsoftwaretoidentifyand measurecellsandotherbiologicalentitiesinimages,toimprovespeed,objectivity,and/orstatisticalpower. Theprincipalinvestigatorenvisionsbringingtransformativeimageanalysisandmachinelearningalgorithms andsoftwaretoawideswathofbiomedicalresearchers.Inadecade,researcherswilltacklefundamentally newproblemswithquantitativeimageanalysis,usingseamlessimagingworkflowsthathavedramaticnew capabilitiesgoingbeyondtheconstraintsofhumanvision. Tothisend,thePIwillcollaboratewithbiologistsonimportantquantitativeimagingprojectsthatalsoyield majoradvancementstotheiropensourceimageanalysissoftware,CellProfiler.Thisversatile,userfriendly softwareisindispensableforbiomedicalresearch.Launched125,000+times/yearworldwide,itiscitedin 3,400+papersfrom1,000+laboratories,impactingahugevarietyofbiomedicalfieldsviaassaysfromcounting cellstoscoringcomplexphenotypesbymachinelearning.CellProfilerevolvesinanintenselycollaborativeand interdisciplinaryresearchenvironmentthathasyieldeddozensofdiscoveriesandseveralpotentialdrugs. Still,manybiologistsaremissingoutonthequantitativebioimagingrevolutionduetolackofeffective algorithmsandusablesoftwarefortheirneeds.InadditiontomaintainingandsupportingCellProfiler,theteam willimplementbiologistrequestedfeatures,algorithms,andinteroperabilitytocopewiththechangingland scapeofmicroscopyexperiments.Challengesincludeincreasesinscale(sometimesmillionsofimages),size (20+GBimages),anddimensionality(timelapse,threedimensional,multispectral).Researchersalsoneedto accommodateavarietyofmodalities(superresolution,singlemolecule,andothers)andintegrateimage analysisintocomplexworkflowswithothersoftwareformicroscopecontrol,cloudcomputing,anddatamining. ThePIwillalsopioneernovelalgorithmsandapproacheschangingthewayimagesareusedinbiology, including:(1)afundamentalredesignoftheimageprocessingworkflowforbiologists,leveragingrevolutionary advancementsindeeplearning,(2)imageanalysisformorephysiologicallyrelevantsystems,suchasmodel organisms,humantissuesamples,andpatientderivedcultures,and(3)datavisualizationandinterpretation softwareforhighdimensionalsinglecellmorphologicalprofiling.Inprofiling,subtlepatternsofmorphological changesincellsaredetectedtoidentifycausesandtreatmentsforvariousdiseases.Wewillalso(4)integrate multipleprofilingdatatypes:morphologywithgeneexpression,epigenetics,andproteomics.Ultimately,we aimtomakeperturbationsincellmorphologyascomputableasotherlargescalefunctionalgenomicsdata. Overall,thelaboratory?sresearchwillyieldhighimpactdiscoveriesfrommicroscopyimages,andits softwarewillenablehundredsofotherNIHfundedlaboratoriestodothesame,acrossallbiologicaldisciplines.
PublicHealthRelevance/Narrative Modernmicroscopyexperimentsareincreasinginscaleandscope?theresearchwillresultinpioneering computationaltechniquesandsoftwarethatwillchangethewaymicroscopyimagesareusedinbiology. Biologistswillusetheresultingsoftwaretotacklefundamentallynewproblemsusingquantitativeimage analysis,includingdetectingchangesintheappearanceofcellsthatareoverlookedbyhumanvisionand studyingintactorganismsandhumantissueratherthanisolatedcells.Themethodswillbedevelopedinthe contextofdozensofprojectsaddressingimportantfundamentalbiologicalquestionsandworldhealth problems,andtheresultingnewfunctionalitywillbeaddedtotheteam?spopular,userfriendly,opensource imageanalysissoftware,CellProfiler.
| Simm, Jaak; Klambauer, Günter; Arany, Adam et al. (2018) Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery. Cell Chem Biol 25:611-618.e3 |
| Vasilevich, Aliaksei S; Mourcin, Frédéric; Mentink, Anouk et al. (2018) Designed Surface Topographies Control ICAM-1 Expression in Tonsil-Derived Human Stromal Cells. Front Bioeng Biotechnol 6:87 |
| Bray, Mark-Anthony; Gustafsdottir, Sigrun M; Rohban, Mohammad H et al. (2017) A dataset of images and morphological profiles of 30 000 small-molecule treatments using the Cell Painting assay. Gigascience 6:1-5 |
