scholarly journals Prognostic Prediction through Biclustering-Based Classification of Clinical Gene Expression Time Series

2011 ◽  
Vol 8 (3) ◽  
pp. 73-89 ◽  
Author(s):  
André V. Carreiro ◽  
Orlando Anunciação ◽  
João A. Carriço ◽  
Sara C. Madeira

Summary The constant drive towards a more personalized medicine led to an increasing interest in temporal gene expression analyzes. It is now broadly accepted that considering a temporal perspective represents a great advantage to better understand disease progression and treatment results at a molecular level. In this context, biclustering algorithms emerged as an important tool to discover local expression patterns in biomedical applications, and CCC-Biclustering arose as an efficient algorithm relying on the temporal nature of data to identify all maximal temporal patterns in gene expression time series. In this work, CCC-Biclustering was integrated in new biclustering-based classifiers for prognostic prediction. As case study we analyzed multiple gene expression time series in order to classify the response of Multiple Sclerosis patients to the standard treatment with Interferon-β, to which nearly half of the patients reveal a negative response. In this scenario, using an effective predictive model of a patient’s response would avoid useless and possibly harmful therapies for the non-responder group. The results revealed interesting potentialities to be further explored in classification problems involving other (clinical) time series.

2003 ◽  
Vol 83 (4) ◽  
pp. 835-858 ◽  
Author(s):  
Harri Lähdesmäki ◽  
Heikki Huttunen ◽  
Tommi Aho ◽  
Marja-Leena Linne ◽  
Jari Niemi ◽  
...  

2008 ◽  
Vol 7 (1) ◽  
pp. 44-55 ◽  
Author(s):  
Zidong Wang* ◽  
Fuwen Yang ◽  
Daniel W. C. Ho ◽  
Stephen Swift ◽  
Allan Tucker ◽  
...  

2007 ◽  
Vol 17 (07) ◽  
pp. 2477-2483 ◽  
Author(s):  
D. REMONDINI ◽  
N. NERETTI ◽  
C. FRANCESCHI ◽  
P. TIERI ◽  
J. M. SEDIVY ◽  
...  

We address the problem of finding large-scale functional and structural relationships between genes, given a time series of gene expression data, namely mRNA concentration values measured from genetically engineered rat fibroblasts cell lines responding to conditional cMyc proto-oncogene activation. We show how it is possible to retrieve suitable information about molecular mechanisms governing the cell response to conditional perturbations. This task is complex because typical high-throughput genomics experiments are performed with high number of probesets (103–104 genes) and a limited number of observations (< 102 time points). In this paper, we develop a deepest analysis of our previous work [Remondini et al., 2005] in which we characterized some of the main features of a gene-gene interaction network reconstructed from temporal correlation of gene expression time series. One first advancement is based on the comparison of the reconstructed network with networks obtained from randomly generated data, in order to characterize which features retrieve real biological information, and which are instead due to the characteristics of the network reconstruction method. The second and perhaps more relevant advancement is the characterization of the global change in co-expression pattern following cMyc activation as compared to a basal unperturbed state. We propose an analogy with a physical system in a critical state close to a phase transition (e.g. Potts ferromagnet), since the cell responds to the stimulus with high susceptibility, such that a single gene activation propagates to almost the entire genome. Our result is relative to temporal properties of gene network dynamics, and there are experimental evidence that this can be related to spatial properties regarding the global organization of chromatine structure [Knoepfler et al., 2006].


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