scholarly journals Microarray Data Analysis: From Hypotheses to Conclusions Using Gene Expression Data

2004 ◽  
Vol 26 (5-6) ◽  
pp. 279-290
Author(s):  
Nicola J. Armstrong ◽  
Mark A. van de Wiel

We review several commonly used methods for the design and analysis of microarray data. To begin with, some experimental design issues are addressed. Several approaches for pre‐processing the data (filtering and normalization) before the statistical analysis stage are then discussed. A common first step in this type of analysis is gene selection based on statistical testing. Two approaches, permutation and model‐based methods are explained and we emphasize the need to correct for multiple testing. Moreover, powerful approaches based on gene sets are mentioned. Clustering of either genes or samples is frequently performed when analyzing microarray data. We summarize the basics of both supervised and unsupervised clustering (classification). The latter may be of use for creating diagnostic arrays, for example. Construction of biological networks, such as pathways, is a statistically challenging but complex task that is a relatively new development and hence mentioned only briefly. We finish with some remarks on literature and software. The emphasis in this paper is on the philosophy behind several statistical issues and on a critical interpretation of microarray related analysis methods.

Test ◽  
2003 ◽  
Vol 12 (1) ◽  
pp. 1-77 ◽  
Author(s):  
Youngchao Ge ◽  
Sandrine Dudoit ◽  
Terence P. Speed

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3593-3593
Author(s):  
Lisa Miller-Phillips ◽  
Volker Heinemann ◽  
Arndt Stahler ◽  
Ludwig Fischer von Weikersthal ◽  
Florian Kaiser ◽  
...  

3593 Background: FIRE-3 compared first-line therapy with FOLFIRI plus cetuximab (cet) or bevacizumab (bev) in KRAS exon 2 wild-type (wt) patients with metastatic colorectal cancer. Recent analyses showed mircoRNA-21 (miR-21) expression level may be a predictive biomarker for anti-EGFR-therapy raising the question whether miR-21 influences gene expression in the EGFR signaling pathway. Methods: Reverse-transcription quantitative polymerase chain reaction assay identified quantitative miR-21 expression. Median expression was defined as a threshold value to discriminate FIRE-3 population into miR-21 low and high groups. Differential gene expression based on additional mRNA microarray data (Almac Inc, Xcel Array) was calculated by linear models adjusted for multiple testing followed by single sample gene set enrichment analysis (ssGSEA) to compare differentially enriched hallmarks of cancer gene sets. Overall response rate (ORR) was compared using Fisher´s exact test. Median progression-free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimation and log-rank test. Results: 333 RAS wt patients provided material for miR-21 expression analysis. In these patients, low miR-21 expression was associated with higher ORR (80.0% vs. 57.9%; p = 0.005) and longer OS (35.8 months (mo) vs. 25.9 mo; p = 0.005) when cet vs bev was added to FOLFIRI. High miR-21 expression was associated with comparable ORR (74.6% vs. 64.0%; p = 0.21) and OS (24.5 mo vs. 23.8 mo; p = 0.4). There was no significant difference in PFS in either group. By comparing miR-21 low and high groups using normalized mRNA microarray data, 538 genes were found to be significantly differentially expressed in RAS wt patients after adjustment for multiple testing. Including data from the two groups into ssGSEA yielded 23 hallmark of cancer gene sets that were significantly differentially enriched; among them, KRAS-signaling showed higher enrichment in the miR-21 high group (adjusted p = 2.09 E-13). Conclusions: MiR-21 expression level might be a predictive biomarker for anti-EGFR-therapy by modulating KRAS signaling in FIRE-3 patients.


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