ArticleBioinformatics (Oxford, England)2011
A framework for analytical characterization of monoclonal antibodies based on reactivity profiles in different tissues.
Article in Bioinformatics (Oxford, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Regulatory T Cells in Melanoma Revisited by a Computational Clustering of FOXP3+ T Cell Subpopulations.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Laser microdissection of the alveolar duct enables single-cell genomic analysis.Frontiers in oncology · 2014Article
- Parametric modeling of cellular state transitions as measured with flow cytometry.BMC bioinformatics · 2012Article
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5 authors.
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Abstract
motivationMonoclonal antibodies (mAbs) are among the most powerful and important tools in biology and medicine. MAb development is of great significance to many research and clinical applications. Therefore, objective mAb classification is essential for categorizing and comparing mAb panels based on their reactivity patterns in different cellular species. However, typical flow cytometric mAb profiles present unique modeling challenges with their non-Gaussian features and intersample variations. It makes accurate mAb classification difficult to do with the currently used kernel-based or hierarchical clustering techniques.
resultsTo address these challenges, in the present study we developed a formal two-step framework called mAbprofiler for systematic, parametric characterization of mAb profiles. Further, we measured the reactivity of hundreds of new antibodies in diverse tissues using flow cytometry, which we successfully classified using mAbprofiler. First, mAbprofiler fits a mAb's flow cytometric histogram with a finite mixture model of skew t distributions that is robust against non-Gaussian features, and constructs a precise, smooth and mathematically rigorous profile. Then it performs novel curve clustering of the fitted mAb profiles using a skew t mixture of non-linear regression model that can handle intersample variation. Thus, mAbprofiler provides a new framework for identifying robust mAb classes, all well defined by distinct parametric templates, which can be used for classifying new mAb samples. We validated our classification results both computationally and empirically using mAb profiles of known classification. AVAILABILITY AND IMPLEMENTATION: A demonstration code in R is available at the journal website. The R code implementing the full framework is available from the author website - http://amath.nchu.edu.tw/www/teacher/tilin/software CONTACT: saumyadipta_pyne@dfci.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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