Significance analysis of lexical bias in microarray data.
BACKGROUND
Genes that are determined to be significantly differentially regulated in microarray analyses often appear to have functional commonalities, such as being components of the same biochemical pathway. This results in certain words being under- or overrepresented in the list of genes. Distinguishing between biologically meaningful trends and artifacts of annotation and analysis procedures is of the utmost importance, as only true biological trends are of interest for further experimentation. A number of sophisticated methods for identification of significant lexical trends are currently available, but these methods are generally too cumbersome for practical use by most microarray users.


RESULTS
We have developed a tool, LACK, for calculating the statistical significance of apparent lexical bias in microarray datasets. The frequency of a user-specified list of search terms in a list of genes which are differentially regulated is assessed for statistical significance by comparison to randomly generated datasets. The simplicity of the input files and user interface targets the average microarray user who wishes to have a statistical measure of apparent lexical trends in analyzed datasets without the need for bioinformatics skills. The software is available as Perl source or a Windows executable.


CONCLUSIONS
We have used LACK in our laboratory to generate biological hypotheses based on our microarray data. We demonstrate the program's utility using an example in which we confirm significant upregulation of SPI-2 pathogenicity island of Salmonella enterica serovar Typhimurium by the cation chelator dipyridyl.
Kim
Charles C
CC
Microbiology and Immunology, Stanford University Medical Center, Stanford, CA, 94305, USA. cckim@stanford.edu
Falkow
Stanley
S
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D016477:Artifacts; D016010:Binomial Distribution; D002614:Chelating Agents / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D044404:Genomic Islands / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data*; D016012:Poisson Distribution; D012107:Research Design / Q000706:statistics & numerical data; D019779:Salmonella enterica / Q000145:classification / Q000187:drug effects / Q000235:genetics; D012703:Serotyping; D012984:Software; D012985:Software Design; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D002614:Chelating Agents; D015082:2,2'-Dipyridyl