iPathwayGuide

iPathwayGuide analyzes gene expression and pathway alterations to identify therapeutic candidates and elucidate mechanisms such as cytokine storm syndrome in SARS‑CoV‑2/COVID‑19.

Key Features:

• Pathway and gene-expression analysis: Performs comprehensive analysis of gene expression alterations and pathway dynamics induced by SARS‑CoV‑2 infection.
• Cell- and tissue-level comparisons: Compares expression changes in NHBE (Normal Human Bronchial Epithelial) cells, A549 lung carcinoma cells, and COVID‑19 affected lung tissues versus respective controls.
• Inflammatory mechanism focus: Targets mechanisms underlying severe inflammatory responses, including cytokine storm syndrome.
• Drug repurposing prioritization: Identifies potential repurposing opportunities among FDA‑approved drugs to mitigate hyper‑inflammation and related symptoms.
• Validation across experimental systems: Supports validation using multiple independent datasets including Vero E6 cells, lung and intestinal organoids, and patient samples.
• Therapeutic candidate output: Reported methylprednisolone (MP) as a prioritized candidate and compared its predicted efficacy to other corticosteroids such as dexamethasone and hydrocortisone.
• Clinical outcome association: Linked predictions to clinical metrics, reporting a reduction in 30‑day all‑cause mortality for MP (29.6% versus 16.6%, P = 0.027) with a number needed to treat (NNT) = 5.

Scientific Applications:

• Drug repurposing for COVID‑19: Prioritizes FDA‑approved drugs for potential mitigation of severe COVID‑19 inflammatory responses.
• Mechanistic studies of hyper‑inflammation: Elucidates pathway-level mechanisms driving cytokine storm syndrome and related severe inflammatory phenotypes.
• Comparative transcriptomics: Enables comparison of gene expression profiles across NHBE, A549, Vero E6, organoids, and patient lung tissues.
• Translational prediction and validation: Generates therapeutic predictions that can be validated across in vitro, organoid, and patient datasets and associated with clinical outcomes.

Methodology:

Performs comprehensive analysis of gene expression alterations and pathway dynamics induced by SARS‑CoV‑2; compares NHBE, A549, and COVID‑19 lung tissues to controls; identifies FDA‑approved drug repurposing candidates; and validates predictions using independent datasets including Vero E6 cells, lung and intestinal organoids, and patient samples.