Bibliometric and visualization analysis of arginine deiminase research from 2006 to 2025: trends, collaboration...

Peptidylarginine Deiminase/Protein Arginine Deiminase (PAD/PADI) are a family of enzymes that catalyze protein citrullination, converting arginine residues to citrulline residues in a calcium-dependent manner. The net loss of positive charge of protein citrullination results in change of conformation, including probable formation of neoepitopes, and interactions with substances like DNA, which contributes to physiologic and pathophysiologic processes such as regulation of gene expression, Neutrophil Extracellular Traps (NETs), Rheumatoid Arthritis (RA), and Multiple Sclerosis (MS). To date, studies of PADs pan- and selective inhibitors have been deepening. This bibliometric analysis tries to give a comprehensive conclusion on research progress of peptidylarginine deiminases (PAD) and PAD inhibitors.

In this study, we aggregated publications using a dual-database strategy (Web of Science and PubMed) from January 1, 2006, to December 5, 2025, with a specific focus on the arginine deiminase research. Utilizing bibliometric methods, the data underwent processing to facilitate visual analysis of various aspects, including countries, institutions, authors, co-citations, keywords, references, gene characteristics, and diseases.

Over the past two decades, the number of publications on the PAD family has increased continuously, with the United States contributing the largest number of publications. The University of Massachusetts emerged as the most prolific institution with 73 publications, while Paul R. Thompson was identified as the leading author in this field. Frontiers in Immunology published the highest number of PAD-related articles. High-frequency keywords included "rheumatoid arthritis", "neutrophil extracellular traps", "citrullination", "PADI", and "arginine deiminase". Recent trends, identified through strong citation bursts from 2022 to 2025, include neutrophil extracellular traps, PADI4, and the tumor microenvironment. The high-frequency genes in the PADs field include PADI4, PADI2, TP53, and MPO. Additionally, pathways such as Lipid and atherosclerosis and viral infection-related pathways are significantly enriched in this research domain.

The research maps the evolving landscape of PAD research over the past two decades. However, cooperation between institutions and countries remains limited, although trends indicate increasing cooperation. This study identifies major research hotspots and evolving trends within the PAD field, helping to guide future research directions and providing an objective, data-driven reference for tracking new frontiers in the field, rather than drawing biological conclusions.