Clarke Labs | Breast Cancer Research

Gene Expression Microarray Studies

Overview

We have begun to apply the technology of gene expression microarrays to identify molecular profiles associated with specific breast cancer phenotypes and responsiveness/resistance to selected systemic therapies in breast cancer. For example, we have optimized a method for the collection and processing of breast core needle biopsies for gene expression profiling (Ellis et al.) and implicated several genes in acquired antiestrogen resistance (Gu et al.).

Working with our colleagues in informatics (Dr. Yue Wang, Computational Bioinformatics and Bioimaging Laboratory (CBIL), Virginia Tech.), biostatistics (Dr. Aiyi Liu, NICHD; Dr. Edmund Gehan, Dr. Antai Wang, Georgetown University; Dr. Bruce Trock, Johns Hopkins University) and medical oncology (Dr. Minetta Liu, Dr. Claudine Issacs, Georgetown University; Dr. Vered Stearns, Johns Hopkins University; Dr. Dan Hayes, University of Michigan) we have continued to develop and apply novel approaches and algorithms for the visualization and analysis of the complex multidimensional data sets generated by this technology (see also Dr. Wang's website).

Selected Publications

Request a reprint (please indicate the reprints you require)

Gene expression profiling, data visualization, data analysis, and related areas from our Bioinformatics and Biostatistics Working Group

Xuan, J., Wang, Y., Hoffman, E., Clarke, R., “Cross phenotype normalization of microarray data.” Front Biosci, in press, 2009.

Chen, L. Xuan, J., Riggins, R.B., Wang, Y. Hoffman, E.P., Riggins, R.B., Clarke, R., “Identification of condition-specific regulatory modules through multi-level motif and mRNA expression analysis,” Int J Comp Biology Drug Design, in press, 2009.

Clarke, R., Shajahan, A.N., Riggins, R.B., Cho, Y., Crawford, A., Xuan, J., Wang, Y., Zwart, A., Nehra, R. & Liu, M.C. “Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cells.” J Steroid Biochem Mol Biol, 114: 8-20, 2009. PubMed

Zhang, B., Li, H., Riggins, R.B., Zhan, M., Xuan, J., Zhang, Z., Hoffman, E.P., Clarke, R., Wang, Y., “Differential dependency network analysis to identify condition-specific topological changes in biological networks” Bioinformatics, 25: 526-532, 2009. PubMed

Chen, L., Xuan, J., Wang, C., Shih, L.-M., Wang, T.-L., Zhang, Z., Clarke, R., Hoffman, E.P. & Wang, Y., “Biomarker identification by knowledge driven multilevel ICA and motif analysis.” Int J Data Mining Bioinformatics, 3: 363-379, 2009.

Olivo, S., Zhu, Y., Lee, R.Y., Cabanes, A., Khan, G., Zwart, A., Wang, Y, Clarke, R., Hilakivi-Clarke, L.A., “Identification of gene signaling pathways mediating the opposite effects of prepubertal low and high fat n-3 PUFA diets on breast cancer risk.” Cancer Prev Res, 1: 522-531, 2008. PubMed

Zhu, Y., Li, H., Miller, D., Wang, Z., Xuan, J., Clarke, R., Hoffman, E.P. & Wang, Y., “caBIG VISDA: modeling, visualization and discovery for cluster analysis of genomic data.” BMC Bioinformatics, 9: 383 (18 pages as published on-line), 2008. PubMed

Chen, L., Xuan, J., Wang, Y., Riggins, R.B., Clarke, R. “Network-constrained support vector machine for classification.” 7th Intl Conf Machine Learning Applications (IMCLA), 60-65, 2008.

Zhang, Y., Xuan, J., de los Reyes, B.G., Clarke, R. & Ressom, H.W. ”Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological data.” BMC Bioinformatics, 9:203 (18 pages as published on-line), 2008. PubMed

Wang, C., Xuan, J., Chen, L., Zhao, P., Wang, Y., Clarke, R., Eric Hoffman, E. “Integrative network component analysis for regulatory network reconstruction.” Proc. 4th Intl Symp Bioinformatics Res Applications (ISBRA), in press, 2008.

Wang, Y., Miller, D.J. & Clarke, R. “Approaches to working in high dimensional data spaces: gene expression microarrays.” Br J Cancer, 98: 1023-1028, 2008. PubMed

Zhu, Y., Wang, Z., Miller, D.J., Clarke, R., Xuan, J., Hoffman, E.P. & Wang, Y. “A ground truth based comparative study on clustering of gene expression data.” Front Biosci, 13: 3839-3849, 2008. PubMed

Clarke, R., Ressom, H., Wang, A., Xuan, J., Liu, M.C., Gehan, E. & Wang, Y. “The properties of high-dimensional data spaces: implications for exploring gene and protein expression data.” Nature Rev Cancer, 8: 37-49, 2008. PubMed

Wang, C., Chen, L., Zhao, P., Hoffman, E., Clarke, R., Wang, Y. & Xuan, J. “Motif-directed component analysis for regulatory network inference.” BMC Bioinformatics, 9: S21 (9 pages as published on-line), 2008. PubMed

Ressom, H.W., Varghese, R.S., Zhang, Z., Xuan, J. & Clarke, R. “Classification algorithms for phenotype prediction in genomics and proteomics.” Front Biosci, 13: 691-708, 2008. PubMed

Gomez, B.P. Riggins, R.B., Shajahan A., Klimach, U., Zhu, Y., Zwart, A., Wang, M., Wang, A. & Clarke, R. “Human X-box binding protein-1 confers both estrogen-independence and antiestrogen resistance in breast cancer.” FASEB J, 21:4013-27, 2007. PubMed

Gong, T., Xuan, J., Wang, C., Li, H., Hoffman, E., Clarke, R. & Wang, Y. “Gene module identification from microarray data using nonnegative independent component analysis.” Gene Regulat Sys Biol, 1: 349-363, 2007. Gene Regulat Sys Biol

Xuan, J., Wang, Y., Dong, Y., Feng, Y., Wang, B., Khan, J., Bakay, M., Wang, Z., Pachman, L., Winokur, S., Chen, Y.-W., Clarke, R., & Hoffman E. “Gene selection for multiclass prediction by weighted Fisher criterion.” EURASIP J Bioinformat System Biol, 2007: Article ID 64628, 15 pages, 2007. PubMed

Xuan, J., Wang, Y., Clarke, R. & Hoffman, E., “An iterative nonlinear regression method for microarray data normalization,” Open Appl Informatics J, 1: 11-19, 2007.

Wang, J., Li, H., Zhu, Y., Yousef, M., Mebozhyn, M., Showe, N., Xuan, J., Clarke, R. & Wang, Y. “VISDA: an open-source caBIG^TManalytical tool for data clustering and beyond.” Bioinformatics, 23: 2024-2027, 2007. PubMed

Ressom, H.W., Zhang, Y., Xuan, J., Wang, Y. & Clarke, R. "Inferring network interactions using recurrent neural networks and swarm intelligence," Proc 28th IEEE EMBS Intl Conf, pp. 4241-4244, 2006. PubMed

Gong, T., Zhu, Y., Xuan, J., Li, H., Clarke, R., Hoffman, E.P. & Wang, Y. “Latent variable and nICA modeling of pathway gene module composite.” Proc 28th IEEE EMBS Intl Conf, pp. 5872-5875, 2006. PubMed

Feng, Y., Wang, Z., Zhu, Y., Xuan, J., Miller, D., Clarke, R., Hoffman, E.P. & Wang, Y. “Learning the tree of phenotypes using genomic data and VISDA.” 6th IEEE Symp Bioinf Bioeng (BIBE´06), 165-170, 2006.

Ressom, H.W., Zhang, Y., Xuan, J., Wang, Y. & Clarke, R. “Inference of gene regulatory networks from time course gene expression data using neural networks and swarm intelligence.” IEEE Symp Compl Intel Bioinf Comput Biol, 435-442, 2006.

Wang, Z., Wang, Y., Xuan, J., Dong, Y., Bakay, M., Khan, J., Clarke, R. & Hoffman, E.P. “Optimized multilayer perceptrons for molecular classification and diagnosis using genomic data.” Bioinformatics, 22: 755-761, 2006. PubMed

Zhu, Y., Wang, A., Liu, M.C., Zwart, A., Lee, R.Y., Gallagher, A., Wang, Y., Miller, W.R., Dixon, J.M. & Clarke, R.“Estrogen receptor alpha (ER) positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structures.” Int J Oncol, 29: 1581-1589, 2006. PubMed

Zhang, J., Huang, K., Khan, J., Li, K., Bhujwalla, Z., Clarke, R., Gu, Z., Szabo, Z., Xuan, J., and Wang, Y. Computational decomposition of molecular signatures. Proc. Intl. Conf. Diagnositic Imaging and Analysis. IEEE press, in Press.

Xuan, J., Dong, Y., Khan, J., Hoffman, E., Clarke, R. & Wang, Y. “Robust feature selection by weighted Fisher criterion for multiclass prediction in gene expression profiling.” Proc Intl Conf Pattern Recon, in press.

Espinoza, L. A., Li, P., Lee, R., Wang, Y., Boulares, A. H., Clarke, R., and Smulson, M. E. "Evaluation of gene expression profiles of keratinocytes in response to JP-8 jet fuel," Toxicoland Appl Pharmacol, 200:93-102, 2004.

Zhang, J., Wang, Y., Khan, J. & Clarke, R. "Gene selection in class space for molecular classification of cancer." Science in China Series F-Information Sciences, 47:301-314, 2004

Wang, Z., Zhang, J., Lu, J., Lee, R., Kung, S.-Y., Clarke R. & Wang Y. Discriminatory mining of gene expression microarray data. J VLSI Signal Process Sys, 35:255-272, 2003. Link to Journal

Liu, A., Zhang, Y., Gehan, E. & Clarke, R. Block principal components analysis with application to gene microarray data classification. Stat Med, 21: 3465-3474, 2002 Link to Abstract (at Statistics in Medicine)

Zhang, J., Huang, K., Khan, J., Li, K., Bhujwalla, Z., Clarke, R., Gu, Z., Szabo, Z., Xuan, J, & Wang, Y. Computational decomposition of molecular signatures. Proc Intl Conf Diagnostic Imaging Analysis, in press. Link to IEEE Publications

Ellis, M., Davis, N., Coop, A., Liu, M., Schumaker, L., Lee, R.Y., Srikanchana, R., Russell, C., Singh, B., Miller, W.R., Stearns, V., Pennanen, M., Tsangaris, T., Gallagher, A., Liu, A., Zwart, A., Hayes, D.F., Lippman, M.E., Wang, Y. & Clarke, R. Development and validation of a method for using breast core needle biopsies for gene expression microarray analyses. Clin Cancer Res, 8: 1155-1166, 2002. Link to Abstract (at Clinical Cancer Research).

Gu, Z., Lee, R.Y., Skaar, T.C., Bouker, K.B., Welch, J.N., Lu, J., Liu, A., Davis, N., Leonessa, F., Brünner, N., Wang, Y. & Clarke, R. Association of interferon regulatory factor-1, nucleophosmin, nuclear factor kappa-B and cAMP response element binding with acquired resistance to Faslodex (ICI 182,780). Cancer Res, 62: 3428-3437, 2002. Link to Abstract (at Cancer Research).

Wang, Y., Lu, J., Lee, R. & Clarke, R. Iterative normalization of cDNA microarray data. IEEE Trans Inf Technol Biomed, 6: 29-37, 2002. Link to Abstract (PubMed).

Lu, J., Wang, Y., Xuan, J., Kung, S.Y., Gu, Z. & Clarke, R. Discriminative analysis of gene microarray data. Proc IEEE Neural Netw Signal Process, 11: 218-227, 2001. Link to IEEE Publications

Skaar, T.C., Prasad, S.C., Sharareh, S., Brünner, N., Lippman, M.E. & Clarke, R. Two-dimensional gel electrophoresis analyses identify nucleophosmin as an estrogen regulated protein associated with acquired estrogen-independence in human breast cancer cells. J Steroid Biochem Mol Biol, 67:391-402, 1998. Link to Abstract (PubMed).

Other manuscripts submitted and in preparation