Psoriasis Transcriptomics: Differential Expression Analysis

A complete RNA-seq data analysis pipeline to characterize the transcriptomic differences and functional implications between healthy skin controls and conventional psoriasis.

About the Report Language

Note: The comprehensive final report associated with this repository (SalazarMendez_Pablo_ProyectoFinal.pdf) is written in Spanish, as it is an academic requirement for the Transcriptomics course at the undergraduate program in Genomic Sciences.

Overview

Psoriasis is a chronic inflammatory skin disease with a complex etiology. This project aims to identify differentially expressed genes (DEGs) between conventional psoriatic skin lesions and normal healthy skin. The analysis reveals a transcriptomic pattern dominated by epidermal and inflammatory activation in psoriasis, alongside a relative decrease in extracellular matrix organization genes.

Dataset

The data was obtained from the Gene Expression Omnibus (GEO) under the accession number GSE117405.

• Total Samples: 17
• Conditions: * 8 Conventional Psoriatic Skin (PS) samples
  • 9 Normal Skin (NS) control samples
• Sequencing Platforms: Illumina HiSeq 2000 & Illumina HiSeq 4000

Pipeline & Methodology

The standard RNA-seq bioinformatics workflow was implemented as follows:

• Quality Control & Trimming: FastQC and fastp (removed 13 initial biased bases).
• Alignment: Reads were aligned to the human reference genome (GRCh38) using STAR.
• Quantification: Read assignment to annotated genomic regions was performed using featureCounts.
• Batch Effect Correction: pyCombat (from the inmoose suite) was used to correct technical variability arising from the different sequencing instruments.
• Differential Expression Analysis: Executed using the DESeq2 implementation in the inmoose Python suite ($FDR < 10^-5$ and $|LFC| > 1$).
• Functional Enrichment: DAVID and STRING were used to analyze DEGs for biological process enrichment and protein-protein interaction (PPI) networks.

Key Results

• Upregulated in Psoriasis: Enrichment in processes related to keratinization, cornified envelope formation, epidermal development, keratinocyte differentiation, innate immunity, and antimicrobial defense (e.g., S100, LCE, and SPRR gene families).
• Downregulated in Psoriasis: Relative reduction in programs associated with extracellular matrix architecture, collagen, cell adhesion, and tissue structural maintenance (e.g., COL5A1, ADAMTS members).

---

Author: Pablo Salazar-Méndez