An active learning approach for rapid characterization of endothelial cells in human tumors.
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Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.
Carcinoma, Renal Cell
Published Version (Please cite this version)10.1371/journal.pone.0090495
Publication InfoCarin, Lawrence; Dipaola, RS; Feldman, MD; Flaherty, KT; Griffith, SD; Heitjan, DF; ... Zhu, Jianliang (2014). An active learning approach for rapid characterization of endothelial cells in human tumors. PLoS One, 9(3). pp. e90495. 10.1371/journal.pone.0090495. Retrieved from http://hdl.handle.net/10161/8940.
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James L. Meriam Professor of Electrical and Computer Engineering
Lawrence Carin earned the BS, MS, and PhD degrees in electrical engineering at the University of Maryland, College Park, in 1985, 1986, and 1989, respectively. In 1989 he joined the Electrical Engineering Department at Polytechnic University (Brooklyn) as an Assistant Professor, and became an Associate Professor there in 1994. In September 1995 he joined the Electrical Engineering Department at Duke University, where he is now a Professor, and Vice Provost for Research. From 2003-2014 he held th
Adjunct Assistant Professor in the Department of Electrical and Computer Engineering
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