AlertGS

AlertGS determines alerts for gene sets by modeling concentration/time-response relationships and applying a Kolmogorov-Smirnoff type test statistic to identify the concentration or time where the first enrichment of a gene set can be observed.

Key Features:

• Gene-wise alert modeling: Models concentration/time-response relationships for individual genes from gene expression experiments measured at multiple concentrations or time points.
• Gene set alert transfer: Transfers the concept of alerts from single genes to gene sets, yielding a global significance statement.
• Kolmogorov-Smirnoff type test statistic: Applies a Kolmogorov-Smirnoff type test statistic for each gene set to determine significance.
• First enrichment identification: Estimates the specific concentration or time where the first enrichment of a gene set can be observed.
• False positive rate control: Controls the false positive rate through subsequent decorrelation approaches.

Scientific Applications:

• Toxicogenomics: Identifies gene sets enriched with significant genes in concentration-response or time-course gene expression studies.
• Gene set enrichment analysis: Provides global significance statements for gene sets in studies with multiple concentrations or time points.
• Alert detection in dose-response studies: Determines the earliest concentration or time point at which a gene set shows significant enrichment.

Methodology:

AlertGS models concentration/time-response relationships for each gene from gene expression experiments, estimates gene-wise alerts, and transfers these alerts to gene sets using a Kolmogorov-Smirnoff type test statistic. Decorrelation approaches are applied to control the false positive rate.