Bibliometrics and Bioinformatics Exploration of Research Hotspots and Key Targets in Comorbidity: Interstitial Lung Disease and Pulmonary Hypertension

Yifei Wang; Wenqi Ji; Liangjie Ma; Xiao Ma

doi:10.3791/71631

A subscription to JoVE is required to view this content. Sign in or start your free trial.

Method Article

Bibliometrics and Bioinformatics Exploration of Research Hotspots and Key Targets in Comorbidity: Interstitial Lung Disease and Pulmonary Hypertension

157 views

⸱

DOI:

10.3791/71631

⸱

August 7th, 2026

Yifei Wang¹^,² , Wenqi Ji³ , Liangjie Ma¹ , Xiao Ma²^,⁴^,⁵

¹Graduate School, Beijing University of Chinese Medicine, ²Physical Examination Center, China-Japan Friendship Hospital, ³Qihuang School, Beijing University of Chinese Medicine, ⁴National Center for Integrative Medicine, China-Japan Friendship Hospital, ⁵School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College

Summary

This protocol uses interstitial lung disease and pulmonary hypertension as examples and integrates bibliometrics with bioinformatics to systematically and preliminarily explore their research trends, hotspots, key targets, and related pathways. This protocol could be replicated to analyze any disease pairs by modifying the prompts.

Abstract

Interstitial lung disease (ILD) and pulmonary hypertension (PH) frequently coexist as comorbidities, leading to poor clinical outcomes and limited therapeutic options. Identifying important research hotspots and uncovering key comorbidity targets is essential for improving disease management and developing novel therapeutic strategies. This protocol retrieves relevant publications from the Web of Science Core Collection and Scopus databases, and uses CiteSpace and VOSviewer to map research hotspots and evolving trends. Subsequently, overlapping genetic targets associated with both diseases are identified from the GeneCards database. Protein-protein interaction networks are constructed using STRING to identify hub genes, and KEGG pathway enrichment analysis is performed using the R language to elucidate key signaling pathways. The results show that bibliometrics identifies the developmental trajectory of this interdisciplinary field from a macro perspective; bioinformatics analysis reveals FN1, IL6, and TNF as potential core comorbidity targets; and KEGG enrichment analysis indicates that immune-related pathways centered on PI3K-Akt and MAPK are deeply involved in the pathogenesis of the comorbidity. By integrating the two approaches, this protocol systematically delineates the development trajectory and research hotspots in ILD-PH comorbidity research, while preliminarily screening potential comorbidity targets and pathways. It provides direction and a computational basis for future experimental research and clinical validation. This integrated framework offers a reproducible methodology applicable to the study of other complex disease comorbidities.

Introduction

Interstitial lung disease (ILD) refers to a group of diffuse lung diseases characterized pathologically by inflammation and fibrosis of the pulmonary interstitium. During its disease progression, it is often complicated by multiple comorbidities, among which pulmonary hypertension (PH) is one of the common comorbidities that significantly affects the prognosis¹^,². Epidemiological data indicate that the incidence of PH in patients with ILD varies depending on the subtype and disease stage, ranging from 13% to 86%³^,⁴^,⁵.....