{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:49:26Z","timestamp":1760150966516,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Algorithms"],"abstract":"<jats:p>Motivation: Precise tracking of individual cells\u2014especially tracking the family lineage, for example in a developing embryo\u2014has widespread applications in biology and medicine. Due to significant noise in microscope images, existing methods have difficulty precisely tracking cell activities. These difficulties often require human intervention to resolve. Humans are helpful because our brain naturally and automatically builds a simulation \u201cmodel\u201d of any scene that we observe. Because we understand simple truths about the world\u2014for example cells can move and divide, but they cannot instantaneously move vast distances\u2014this model \u201cin our heads\u201d helps us to severely constrain the possible interpretations of what we see, allowing us to easily distinguish signal from noise, and track the motion of cells even in the presence of extreme levels of noise that would completely confound existing automated methods. Results: Here, we mimic the ability of the human brain by building an explicit computer simulation model of the scene. Our simulated cells are programmed to allow movement and cell division consistent with reality. At each video frame, we stochastically generate millions of nearby \u201cUniverses\u201d and evolve them stochastically to the next frame. We then find and fit the best universes to reality by minimizing the residual between the real image frame and a synthetic image of the simulation. The rule-based simulation puts extremely stringent constraints on possible interpretations of the data, allowing our system to perform far better than existing methods even in the presense of extreme levels of image noise. We demonstrate the viability of this method by accurately tracking every cell in a colony that grows from 4 to over 300 individuals, doing about as well as a human can in the difficult task of tracking cell lineages.<\/jats:p>","DOI":"10.3390\/a15020051","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T01:46:08Z","timestamp":1643593568000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["No Cell Left behind: Automated, Stochastic, Physics-Based Tracking of Every Cell in a Dense, Growing Colony"],"prefix":"10.3390","volume":"15","author":[{"given":"Huy","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emile R.","family":"Shehada","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawna","family":"Stahlheber","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kushagra","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3310-6042","authenticated-orcid":false,"given":"Wayne B.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3233\/FI-2020-1887","article-title":"A survey on nature-inspired medical image analysis: A step further in biomedical data integration","volume":"171","author":"Rundo","year":"2020","journal-title":"Fundam. Inform."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.media.2008.06.001","article-title":"Cell Population Tracking and Lineage Construction with Spatiotemporal Context","volume":"12","author":"Li","year":"2008","journal-title":"Med. Image Anal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1093\/bioinformatics\/btu080","article-title":"A benchmark for comparison of cell tracking algorithms","volume":"30","author":"Ulman","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.semcdb.2009.07.004","article-title":"Tracking in cell and developmental biology","volume":"20","author":"Meijering","year":"2009","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1109\/TMI.2009.2027813","article-title":"Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis","volume":"29","author":"Li","year":"2010","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.4161\/cc.5.3.2426","article-title":"Automated cell lineage construction: A rapid method to analyze clonal development established with murine neural progenitor cells","volume":"5","author":"Radke","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101575","DOI":"10.1016\/j.bspc.2019.101575","article-title":"Split and merge watershed: A two-step method for cell segmentation in fluorescence microscopy images","volume":"53","author":"Gamarra","year":"2019","journal-title":"Biomed. Signal Process. Control"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13626","DOI":"10.1073\/pnas.1001651107","article-title":"Collective motion and density fluctuations in bacterial colonies","volume":"107","author":"Zhang","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.media.2010.07.006","article-title":"Coupled minimum-cost flow cell tracking for high-throughput quantitative analysis","volume":"15","author":"Padfield","year":"2011","journal-title":"Med. Image Anal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1093\/bioinformatics\/btn247","article-title":"CellTrack: An open-source software for cell tracking and motility analysis","volume":"24","author":"Sacan","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_11","first-page":"e863564","article-title":"Cellcounter: Novel Open-Source Software for Counting Cell Migration and Invasion In Vitro","volume":"2014","author":"Li","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R100","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: Image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"Carpenter","year":"2006","journal-title":"Genome Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2144\/000112257","article-title":"CellProfiler: Free, versatile software for automated biological image analysis","volume":"42","author":"Lamprecht","year":"2007","journal-title":"BioTechniques"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/nmeth.1237","article-title":"Robust single particle tracking in live cell time-lapse sequences","volume":"5","author":"Jaqaman","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1365-2818.2011.03529.x","article-title":"Automated and semi-automated cell tracking: Addressing portability challenges","volume":"244","author":"Kan","year":"2011","journal-title":"J. Microsc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36984","DOI":"10.1038\/srep36984","article-title":"Lineage mapper: A versatile cell and particle tracker","volume":"6","author":"Chalfoun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, B., Zimmer, C., and Olivo-Marin, J.C. (2004, January 18). Tracking fluorescent cells with coupled geometric active contours. Proceedings of the 2004 2nd IEEE International Symposium on Biomedical Imaging: Nano to Macro, Arlington, VA, USA.","DOI":"10.1109\/ISBI.2004.1398578"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1098\/rsif.2014.0386","article-title":"Automated, contour-based tracking and analysis of cell behaviour over long time scales in environments of varying complexity and cell density","volume":"11","author":"Baker","year":"2014","journal-title":"J. R. Soc. Interface"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1093\/bioinformatics\/btq434","article-title":"Automated analysis of time-lapse fluorescence microscopy images: From live cell images to intracellular foci","volume":"26","author":"Dzyubachyk","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1109\/TMI.2013.2243463","article-title":"Segmentation and Shape Tracking of Whole Fluorescent Cells Based on the Chan-Vese Model","volume":"32","author":"Danek","year":"2013","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_21","first-page":"101","article-title":"Cell Segmentation Using Coupled Level Sets and Graph-Vertex Coloring","volume":"9","author":"Nath","year":"2006","journal-title":"Med. Image Comput. Comput. Assist. Interv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1175\/2007MWR2018.1","article-title":"Ensemble Data Assimilation with the NCEP Global Forecast System","volume":"136","author":"Whitaker","year":"2008","journal-title":"Mon. Weather. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/qj.751","article-title":"The Central European limited-area ensemble forecasting system: ALADIN-LAEF","volume":"137","author":"Wang","year":"2011","journal-title":"Q. J. R. Meteorol. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.envhaz.2007.05.001","article-title":"Ensemble predictions and perceptions of risk, uncertainty, and error in flood forecasting","volume":"7","author":"Demeritt","year":"2007","journal-title":"Environ. Hazards"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1175\/1520-0477(2001)082<2377:ESOTFC>2.3.CO;2","article-title":"Ensemble simulation of twenty\u2013first century climate changes: Business\u2013as\u2013usual versus CO2 stabilization","volume":"82","author":"Dai","year":"2001","journal-title":"Bull. Am. Meteorol. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1109\/TPAMI.2013.97","article-title":"Multiple Hypothesis Tracking for Cluttered Biological Image Sequences","volume":"35","author":"Chenouard","year":"2013","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/mmi.13486","article-title":"SuperSegger: Robust image segmentation, analysis and lineage tracking of bacterial cells: Robust segmentation and analysis of bacteria","volume":"102","author":"Stylianidou","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1093\/bioinformatics\/bts424","article-title":"Tlm-tracker: Software for cell segmentation, tracking and lineage analysis in time-lapse microscopy movies","volume":"28","author":"Klein","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/mmi.13264","article-title":"Oufti: An integrated software package for high-accuracy, high-throughput quantitative microscopy analysis","volume":"99","author":"Paintdakhi","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","article-title":"TrackMate: An open and extensible platform for single-particle tracking","volume":"115","author":"Tinevez","year":"2017","journal-title":"Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cmpb.2011.06.002","article-title":"Timelapseanalyzer: Multi-target analysis for live-cell imaging and time-lapse microscopy","volume":"104","author":"Huth","year":"2011","journal-title":"Comput. Methods Programs Biomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1093\/bioinformatics\/btw406","article-title":"Lever: Software tools for segmentation, tracking and lineaging of proliferating cells","volume":"32","author":"Winter","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.gde.2017.01.002","article-title":"Recent progress in single-cell cancer genomics","volume":"42","author":"Tsoucas","year":"2017","journal-title":"Curr. Opin. Genet. 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