Connecting omics signatures of diseases, drugs, and mechanisms of actions with iLINCS

Abstract

iLINCS (http://ilincs.org) is an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The portal facilitates analysis of user-submitted omics signatures of diseases and cellular perturbations in the context of a large compendium of precomputed signatures (>200,000), as well as mining and re-analysis of the large collection of omics datasets (>10,000), pre-computed signatures and their connections. Analytics workflows driven by user-friendly interfaces enable users with only conceptual understanding of the analysis strategy to execute sophisticated analyses of omics signatures, such as systems biology analysis and interpretation of signatures, mechanism of action analysis and signature-driven drug repositioning. iLINCS workflows integrate a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. There are only few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require any computer programming skills. Among them, iLINCS is unique in terms of the scope and versatility of the data it provides and the analytics it facilitates.

Therapeutic Approaches for COVID-19 Based on the Dynamics of Interferon-mediated Immune Responses

“…At first, "coronavirus" was searched through iLINCS at http://ilincs.org (20). pathway databases were used for pathway enrichment analysis to assess the potential association of the signature with pathways.…”

“…In a study 39 To validate this assumption, the dataset of the above-mentioned study (41), GDS1028, was searched and reanalyzed with the help of iLINCS (42). Noteworthy, this dataset contains the expression profiling of peripheral blood mononuclear cells (PBMC) from 10 adult hospitalized patients with SARS and four healthy controls.…”

Predicting mechanism of action of cellular perturbations with pathway activity signatures

“…Correlating CP transcriptional signature with the signatures of genetic perturbations of genes in the pathway (Pilarczyk, et al, 2019;Subramanian, et al, 2017). The use of GP signatures provides information about the activity changes in signaling proteins not contained in the CP transcriptional signature alone.…”

“…Gene expression changes after shRNA-or CRISPR-based knockdown of a gene can be used to precisely define a transcriptional signature of protein inactivation (Bild, et al, 2006). The concordance between such a genetic perturbation (GP) transcriptional signature and a transcriptional signature of a chemical perturbagen (CP), indicates the plausibility that the CP is perturbing the activity of the protein (Pilarczyk, et al, 2019;Subramanian, et al, 2017). In addition to CP signatures, recently released L1000 dataset generated by the LINCS project (Library of Integrated Network-based Cellular Signature) provides genetic perturbation signatures consisting of averaged changes in gene expression after knocking down the same gene with multiple shRNA's for more than 3,500 human genes, perturbed in several cancer cell lines (Subramanian, et al, 2017).…”

“…The key innovation of our methodology is the integration of two distinct strategies for implicating MOA of a chemical perturbagen: the topological pathway analysis (Mitrea, et al, 2013) and use of LINCS GP signatures (Pilarczyk, et al, 2019;Subramanian, et al, 2017). The integration is facilitated by an innovative statistical learning approach that uses the information about the topology of protein-protein interactions within a pathway and the LINCS GP signatures of the genes in the pathway to construct a pathway activity signature (PAS).…”