Interpreting Patterns of Gene Expression with Self-Organizing Maps: Methods and Application to Hematopoietic Differentiation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 6; pp. 2907 - 2912
• Main Authors: Tamayo, Pablo, Slonim, Donna, Mesirov, Jill, Zhu, Qing, Kitareewan, Sutisak, Dmitrovsky, Ethan, Lander, Eric S., Golub, Todd R.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 16-03-1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Analysis; Animals; Biological Sciences; Cell cycle; Cell lines; Cluster Analysis; Datasets; Gene expression; Gene Expression Regulation; Genes; Genetic variation; Genetics; Hematopoiesis - genetics; HL-60 Cells; Humans; Jurkat Cells; Macrophages; Neutrophils; Online data bases; Saccharomyces cerevisiae; Software; T lymphocytes; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.6.2907

Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of self-organizing maps, a type of mathematical cluster analysis that is particularly well suited for recognizing and classifying features in complex, multidimensional data. The method has been implemented in a publicly available computer package, GENECLUSTER, that performs the analytical calculations and provides easy data visualization. To illustrate the value of such analysis, the approach is applied to hematopoietic differentiation in four well studied models (HL-60, U937, Jurkat, and NB4 cells). Expression patterns of some 6,000 human genes were assayed, and an online database was created. GENECLUSTER was used to organize the genes into biologically relevant clusters that suggest novel hypotheses about hematopoietic differentiation--for example, highlighting certain genes and pathways involved in "differentiation therapy" used in the treatment of acute promyelocytic leukemia.