Ranking, selecting, and prioritising genes with desirability functions.
1In Silico Lead Discovery, Novartis Institutes for Biomedical Research , Basel , Switzerland.
Peerj
|December 9, 2015
Summary
Researchers can improve gene selection in functional genomics by using desirability functions. This approach integrates multiple criteria for ranking genes, moving beyond simple thresholds to enhance discovery and prioritize key genes effectively.
Area of Science:
- Genomics
- Bioinformatics
- Biostatistics
Background:
- Functional genomics experiments generate large datasets of differentially expressed genes.
- Traditional gene selection methods rely on arbitrary thresholds (p-values, fold-changes) and ad hoc criteria, which can be inefficient and overlook relevant genes.
- Current methods do not adequately account for measurement uncertainty or integrate diverse data sources.
Purpose of the Study:
- To introduce and demonstrate the utility of desirability functions for a more robust and integrated approach to gene selection in functional genomics.
- To provide a flexible framework for ranking and prioritizing genes based on multiple criteria, including experimental results and database information.
- To address the limitations of conventional threshold-based gene selection methods.
Main Methods:
- Desirability functions are employed to map various selection criteria (p-values, fold-changes, etc.) onto a continuous 0-1 scale, where 1 represents maximum desirability.
- Multiple criteria are combined to calculate an overall desirability score for each gene.
- A breast cancer microarray dataset is used to illustrate the application of the desirability function approach for gene prioritization.
Main Results:
- The desirability function approach allows for the integration of multiple data types and experimental outcomes into a single ranking metric.
- This method provides a more nuanced prioritization of genes compared to traditional binary thresholding.
- The approach demonstrated effective gene selection and prioritization in a real-world breast cancer dataset.
Conclusions:
- Desirability functions offer an efficient and flexible alternative to traditional gene selection methods in functional genomics.
- This approach enhances the ability to identify and prioritize relevant genes by comprehensively integrating diverse data and accounting for uncertainty.
- The desiR R package is available to facilitate the implementation of this method for researchers.
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