Prioritizing susceptibility genes for the prognosis of male-pattern baldness with transcriptome-wide association study.

BACKGROUND: Male-pattern baldness (MPB) is the most common cause of hair loss in men. It can be categorized into three types: type 2 (T2), type 3 (T3), and type 4 (T4), with type 1 (T1) being considered normal. Although various MPB-associated genetic variants have been suggested, a comprehensive study for linking these variants to gene expression regulation has not been performed to the best of our knowledge. RESULTS: In this study, we prioritized MPB-related tissue panels using tissue-specific enrichment analysis and utilized single-tissue panels from genotype-tissue expression version 8, as well as cross-tissue panels from context-specific genetics. Through a transcriptome-wide association study and colocalization analysis, we identified 52, 75, and 144 MPB associations for T2, T3, and T4, respectively. To assess the causality of MPB genes, we performed a conditional and joint analysis, which revealed 10, 11, and 54 putative causality genes for T2, T3, and T4, respectively. Finally, we conducted drug repositioning and identified potential drug candidates that are connected to MPB-associated genes. CONCLUSIONS: Overall, through an integrative analysis of gene expression and genotype data, we have identified robust MPB susceptibility genes that may help uncover the underlying molecular mechanisms and the novel drug candidates that may alleviate MPB.

A Transcriptome-Wide Analysis of Psoriasis: Identifying the Potential Causal Genes and Drug Candidates.

Psoriasis is a chronic inflammatory skin disease characterized by cutaneous eruptions and pruritus. Because the genetic backgrounds of psoriasis are only partially revealed, an integrative and rigorous study is necessary. We conducted a transcriptome-wide association study (TWAS) with the new Genotype-Tissue Expression version 8 reference panels, including some tissue and multi-tissue panels that were not used previously. We performed tissue-specific heritability analyses on genome-wide association study data to prioritize the tissue panels for TWAS analysis. TWAS and colocalization (COLOC) analyses were performed with eight tissues from the single-tissue panels and the multi-tissue panels of context-specific genetics (CONTENT) to increase tissue specificity and statistical power. From TWAS, we identified the significant associations of 101 genes in the single-tissue panels and 64 genes in the multi-tissue panels, of which 26 genes were replicated in the COLOC. Functional annotation and network analyses identified that the genes were associated with psoriasis and/or immune responses. We also suggested drug candidates that interact with jointly significant genes through a conditional and joint analysis. Together, our findings may contribute to revealing the underlying genetic mechanisms and provide new insights into treatments for psoriasis.

Elucidating immunological characteristics of the adenoma-carcinoma sequence in colorectal cancer patients in South Korea using a bioinformatics approach.

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.

Meta-analysis of single-cell RNA-sequencing data for depicting the transcriptomic landscape of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by airflow limitation and chronic inflammation of the lungs that is a leading cause of death worldwide. Since the complete pathological mechanisms at the single-cell level are not fully understood yet, an integrative approach to characterizing the single-cell-resolution landscape of COPD is required. To identify the cell types and mechanisms associated with the development of COPD, we conducted a meta-analysis using three single-cell RNA-sequencing datasets of COPD. Among the 154,011 cells from 16 COPD patients and 18 healthy subjects, 17 distinct cell types were observed. Of the 17 cell types, monocytes, mast cells, and alveolar type 2 cells (AT2 cells) were found to be etiologically implicated in COPD based on genetic and transcriptomic features. The most transcriptomically diversified states of the three etiological cell types showed significant enrichment in immune/inflammatory responses (monocytes and mast cells) and/or mitochondrial dysfunction (monocytes and AT2 cells). We then identified three chemical candidates that may potentially induce COPD by modulating gene expression patterns in the three etiological cell types. Overall, our study suggests the single-cell level mechanisms underlying the pathogenesis of COPD and may provide information on toxic compounds that could be potential risk factors for COPD.