Computational synchronization of microarray data with application to Plasmodium falciparum
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Author(s) • • •
Zhao, Wei
Dauwels, Justin H. G.
Niles, Jacquin
Cao, Jianshu
Date Issued
June 2012
Journal
Proteome Science
Publisher
BioMed Central Ltd
Citation
Zhao, Wei et al. “Computational Synchronization of Microarray Data with Application to Plasmodium Falciparum.” Proteome Science 10.Suppl 1 (2012): S10. Web.
Version
Final published version
Abstract
Background Microarrays are widely used to investigate the blood stage of Plasmodium falciparum infection. Starting with synchronized cells, gene expression levels are continually measured over the 48-hour intra-erythrocytic cycle (IDC). However, the cell population gradually loses synchrony during the experiment. As a result, the microarray measurements are blurred. In this paper, we propose a generalized deconvolution approach to reconstruct the intrinsic expression pattern, and apply it to P. falciparum IDC microarray data. Methods We develop a statistical model for the decay of synchrony among cells, and reconstruct the expression pattern through statistical inference. The proposed method can handle microarray measurements with noise and missing data. The original gene expression patterns become more apparent in the reconstructed profiles, making it easier to analyze and interpret the data. We hypothesize that reconstructed gene expression patterns represent better temporally resolved expression profiles that can be probabilistically modeled to match changes in expression level to IDC transitions. In particular, we identify transcriptionally regulated protein kinases putatively involved in regulating the P. falciparum IDC. Results By analyzing publicly available microarray data sets for the P. falciparum IDC, protein kinases are ranked in terms of their likelihood to be involved in regulating transitions between the ring, trophozoite and schizont developmental stages of the P. falciparum IDC. In our theoretical framework, a few protein kinases have high probability rankings, and could potentially be involved in regulating these developmental transitions. Conclusions This study proposes a new methodology for extracting intrinsic expression patterns from microarray data. By applying this method to P. falciparum microarray data, several protein kinases are predicted to play a significant role in the P. falciparum IDC. Earlier experiments have indeed confirmed that several of these kinases are involved in this process. Overall, these results indicate that further functional analysis of these additional putative protein kinases may reveal new insights into how the P. falciparum IDC is regulated.
Description
From IEEE International Conference on Bioinformatics and Biomedicine 2011
Atlanta, GA, USA. 12-15 November 2011
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
Singapore-MIT Alliance in Research and Technology (SMART)
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DOI of Published Version
https://doi.org/10.1186/1477-5956-10-S1-S10