IRIS3 – integrated cell-type-specific regulon inference server from single-cell RNA-Seq

A group of genes controlled as a unit, usually by the same repressor or activator gene, is known as a regulon. The ability to identify active regulons within a specific cell type, i.e., cell-type-specific regulons (CTSR), provides an extraordinary opportunity to pinpoint crucial regulators and target genes responsible for complex diseases. However, the identification of CTSRs from single-cell RNA-Seq (scRNA-Seq) data is computationally challenging.

Researchers from The Ohio State University have developed IRIS3, the first-of-its-kind web server for CTSR inference from scRNA-Seq data for human and mouse. IRIS3 is an easy-to-use server empowered by over 20 functionalities to support comprehensive interpretations and graphical visualizations of identified CTSRs. CTSR data can be used to reliably characterize and distinguish the corresponding cell type from others and can be combined with other computational or experimental analyses for biomedical studies. CTSRs can, therefore, aid in the discovery of major regulatory mechanisms and allow reliable constructions of global transcriptional regulation networks encoded in a specific cell type. The broader impact of IRIS3 includes, but is not limited to, investigation of complex diseases hierarchies and heterogeneity, causal gene regulatory network construction, and drug development.

The workflow of IRIS3

The workflow of IRIS3. The only required input is the scRNA-Seq expression matrix. Seven steps are used to infer CTSRs. A user can upload reference gene modules (lists) for an additional CTSR inference, and the uploaded cell labels can be used as a benchmark for predicted cell type evaluation and substitution for CTSR inference. The output report, along with a unique job ID, will be generated and emailed to the user once the analysis is complete.

The only required input is the scRNA-Seq expression matrix. Seven steps are used to infer CTSRs. A user can upload reference gene modules (lists) for an additional CTSR inference, and the uploaded cell labels can be used as a benchmark for predicted cell type evaluation and substitution for CTSR inference. The output report, along with a unique job ID, will be generated and emailed to the user once the analysis is complete.

Availability – IRIS3 is freely accessible from https://bmbl.bmi.osumc.edu/iris3/ with no login requirement.

Ma A, Wang C, Chang Y, Brennan FH, McDermaid A, Liu B, Zhang C, Popovich PG, Ma Q. (2020) IRIS3: integrated cell-type-specific regulon inference server from single-cell RNA-Seq. Nucleic Acids Res [Epub ahead of print]. [article]

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