Human Molecular Genetics, 1999, Vol. 8, No. 10 1821-1832
© 1999 Oxford University Press
Review |
Computational methods for theidentification of differential and coordinated gene expression
Structural and Genetic Information Laboratory, CNRS UMR1889, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France
ABSTRACT
With the first complete ‘draft’ ofthe human genome sequence expected for Spring 2000, the three basicchallenges for today’s bioinformatics are more than ever:(i) finding the genes; (ii) locating their coding regions; and (iii) predictingtheir functions. However, our capacity for interpreting vertebrategenomic and transcript (cDNA) sequences using experimental or computationalmeans very much lags behind our raw sequencing power. If the performancesof current programs in identifying internal coding exons are good,the precise 5'
3' delineationof transcription units (and promoters) still requires additionalexperiments. Similarly, functional predictions made with referenceto previously characterized homologues are leaving >50% ofhuman genes unannotated or classified in uninformative categories(‘kinase’, ‘ATP-binding’, etc.).In the context of functional genomics, large-scale gene expressionstudies using massive cDNA tag sequencing, two-dimensional gel proteomeanalysis or microarray technologies are the only approaches providinggenome-scale experimental information at a pace consistent withthe progress of sequencing. Given the difficulty and cost of characterizinggenes one by one, academic and industrial researchers are increasinglyrelying on those methods to prioritize their studies and choosetheir targets. The study of expression patterns can also providesome insight into the function, reveal regulatory pathways, indicateside effects of drugs or serve as a diagnostic tool. In this article,I review the theoretical and computational approaches used to: (i)identify genes differentially expressed (across cell types, developmentalstages, pathological conditions, etc.); (ii) identify genes expressedin a coordinated manner across a set of conditions; and (iii) delineateclusters of genes sharing coherent expression features, eventuallydefining global biological pathways.
FOOTNOTES
a Tel: +334 91 16 45 48; Fax: +33 4 91 16 45 49; Email: jmc{at}igs.cnrs-mrs.fr
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