Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers.
作者： SChakra Chennubhotla , DanielM Spagnolo , Rekha Gyanchandani , Yousef Al-Kofahi , AndrewM Stern
关键词:
摘要: Background: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including stromal in the tumor microenvironment (TME) key contributors heterogeneity. Methods: We demonstrate how quantify from immunofluorescence pathology samples, using a set 3 basic breast as test case. learn dominant biomarker intensity patterns map distribution with network. then describe pairwise association statistics each pattern within network pointwise mutual information (PMI) visually represent two-dimensional map. Results: found salient 8 cellular phenotypes tissue microarray cohort containing 4 different subtypes. After computing PMI pair patient replicate, we visualize interactions that contribute resulting statistics. Then, potential biomarker, by comparing maps scores patients across Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited highest score those tested, while estrogen negative ductal AL13-14, lowest score. Conclusions: This paper presents an approach describing heterogeneity, quantitative fashion (via PMI), which departs purely qualitative approaches currently used clinic. is generalizable highly multiplexed/hyperplexed images, well data complementary situ methods FISSEQ CyTOF, sampling many components TME. hypothesize will uncover TME disease proliferation progression.
jpathinformatics.org
core.ac.uk 参考文章(43)
Ali Bashashati, Gavin Ha, Alicia Tone, Jiarui Ding, Leah M Prentice, Andrew Roth, Jamie Rosner, Karey Shumansky, Steve Kalloger, Janine Senz, Winnie Yang, Melissa McConechy, Nataliya Melnyk, Michael Anglesio, Margaret TY Luk, Kane Tse, Thomas Zeng, Richard Moore, Yongjun Zhao, Marco A Marra, Blake Gilks, Stephen Yip, David G Huntsman, Jessica N McAlpine, Sohrab P Shah, None, Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling The Journal of Pathology. ,vol. 231, pp. 21- 34 ,(2013) , 10.1002/PATH.4230
Doris P. Tabassum, Kornelia Polyak, Tumorigenesis: it takes a village Nature Reviews Cancer. ,vol. 15, pp. 473- 483 ,(2015) , 10.1038/NRC3971
Yousef Al-Kofahi, Wiem Lassoued, Kedar Grama, Sumit K Nath, Jianliang Zhu, Ridha Oueslati, Michael Feldman, William M F Lee, Badrinath Roysam, Cell-based quantification of molecular biomarkers in histopathology specimens Histopathology. ,vol. 59, pp. 40- 54 ,(2011) , 10.1111/J.1365-2559.2011.03878.X
Robert J. Steininger, Satwik Rajaram, Luc Girard, John D. Minna, Lani F. Wu, Steven J. Altschuler, On comparing heterogeneity across biomarkers Cytometry Part A. ,vol. 87, pp. 558- 567 ,(2015) , 10.1002/CYTO.A.22599
Ash A Alizadeh, Victoria Aranda, Alberto Bardelli, Cedric Blanpain, Christoph Bock, Christine Borowski, Carlos Caldas, Andrea Califano, Michael Doherty, Markus Elsner, Manel Esteller, Rebecca Fitzgerald, Jan O Korbel, Peter Lichter, Christopher E Mason, Nicholas Navin, Dana Pe'Er, Kornelia Polyak, Charles WM Roberts, Lillian Siu, Alexandra Snyder, Hannah Stower, Charles Swanton, Roel GW Verhaak, Jean C Zenklusen, Johannes Zuber, Jessica Zucman-Rossi, None, Toward understanding and exploiting tumor heterogeneity Nature Medicine. ,vol. 21, pp. 846- 853 ,(2015) , 10.1038/NM.3915
Yutaka Sugihara, Hirokazu Taniguchi, Ryoji Kushima, Hitoshi Tsuda, Daisuke Kubota, Hiroshi Ichikawa, Shin Fujita, Tadashi Kondo, Laser microdissection and two-dimensional difference gel electrophoresis reveal proteomic intra-tumor heterogeneity in colorectal cancer. Journal of Proteomics. ,vol. 78, pp. 134- 147 ,(2013) , 10.1016/J.JPROT.2012.11.009
F. R. Balkwill, M. Capasso, T. Hagemann, The tumor microenvironment at a glance Journal of Cell Science. ,vol. 125, pp. 5591- 5596 ,(2012) , 10.1242/JCS.116392
Jonathan M Irish, Randi Hovland, Peter O Krutzik, Omar D Perez, Øystein Bruserud, Bjørn T Gjertsen, Garry P Nolan, Single Cell Profiling of Potentiated Phospho-Protein Networks in Cancer Cells Cell. ,vol. 118, pp. 217- 228 ,(2004) , 10.1016/J.CELL.2004.06.028
Robert L. Camp, Gina G. Chung, David L. Rimm, Automated subcellular localization and quantification of protein expression in tissue microarrays. Nature Medicine. ,vol. 8, pp. 1323- 1327 ,(2002) , 10.1038/NM791
Ashley G. Rivenbark, Siobhan M. O’Connor, William B. Coleman, Molecular and cellular heterogeneity in breast cancer: challenges for personalized medicine. American Journal of Pathology. ,vol. 183, pp. 1113- 1124 ,(2013) , 10.1016/J.AJPATH.2013.08.002