Exploring research hotspots and future directions in neural tube defects field by bibliometric and bioinformatics analysis

Abstract

Background: Neural tube defects (NTDs) is the most common birth defect of the central nervous system (CNS) which causes the death of almost 88,000 people every year around the world. Much efforts have been made to investigate the reasons that contribute to NTD and explore new ways to for prevention. We trawl the past decade (2013-2022) published records in order to get a worldwide view about NTDs research field.

Methods: 7,437 records about NTDs were retrieved from the Web of Science (WOS) database. Tools such as shell scripts, VOSviewer, SCImago Graphica, CiteSpace and PubTator were used for data analysis and visualization.

Results: Over the past decade, the number of publications has maintained an upward trend, except for 2022. The United States is the country with the highest number of publications and also with the closest collaboration with other countries. Baylor College of Medicine has the closest collaboration with other institutions worldwide and also was the most prolific institution. In the field of NTDs, research focuses on molecular mechanisms such as genes and signaling pathways related to folate metabolism, neurogenic diseases caused by neural tube closure disorders such as myelomeningocele and spina bifida, and prevention and treatment such as folate supplementation and surgical procedures. Most NTDs related genes are related to development, cell projection parts, and molecular binding. These genes are mainly concentrated in cancer, Wnt, MAPK, PI3K-Akt and other signaling pathways. The distribution of NTDs related SNPs on chromosomes 1, 3, 5, 11, 14, and 17 are relatively concentrated, which may be associated with high-risk of NTDs.

Conclusion: Bibliometric analysis of the literature on NTDs field provided the current status, hotspots and future directions to some extant. Further bioinformatics analysis expanded our understanding of NTDs-related genes function and revealed some important SNP clusters and loci. This study provided some guidance for further studies. More extensive cooperation and further research are needed to overcome the ongoing challenge in pathogenesis, prevention and treatment of NTDs.

Keywords: bibliometric; bioinformatics; gene; neural tube defects (NTDs); single nucleotide polymorphism (SNP).

Figure 1

Overall, there has been a growing trend of publication in the field of NTDs in the last decade. Globally, the United States (USA) has the most extensive partnerships with other countries with the highest number of papers published. (A) Annual publication volumes in the field of NTDs from 2013–2022. (B) The national cooperation network. Different colors represent different cooperation intensity, and the size of the dots represents the number of publications. The names of the top 30 countries with most publications are displayed. (C) Top 10 countries with most publications.

Figure 2

Countries around the world are clustered into six groups to cooperate with each other, with the United States cooperating most closely with other countries. (A) Countries collaboration network, within six clusters. Different colors represent different clusters, and the size of the dots represents the number of publications. (B) Cooperation intensity map of 61 countries, different colors represent different cooperation intensity, and the size of the dots represents the number of publications.

Figure 3

Institutions around the world are clustered into eight groups to cooperate with each other. Baylor college of medicine has the most extensive partnerships with other institutions with the highest number of papers published. (A) Institutions collaboration network, within eight clusters. Different colors represent different clusters, and the size of the dots represents the number of publications. (B) Top 10 institutions with most publications. Most of them are located in the United States (USA). (C) Top 10 institutions with most total link strength. Nine of them are located in the United States (USA).

Figure 4

Authors are clustered into seven groups to cooperate with each other. In the top 10 list of publication and collaboration intensity, most authors are from China. (A) Author cooperative network. Different colors represent different clusters, and the size of the dots represents the number of publications. (B) Top 10 authors with most number of papers published. Most of them are from China. (C) Top 10 authors with most total link strength. All of them are from China.

Figure 5

Keyword analysis indicated the research fronts and trend. (A,B) Keyword co-occurrence (A) and keyword density map (B). They were constructed by Vosviewer. (C) Keyword timeline map visualized by Citespace. These results shown in panels (A–C) pointed that researches in NTDs field were focus on the genetic and non-genetic causes, the prenatal repair and postnatal treatment for major clinical phenotypes and molecular mechanisms of folic acid prevention. (D) Top 25 burst keywords in the field of NTDs. In the past 3 years, keywords like “therapy,” “first trimester,” “in utero repair,” “fatal surgery” were with the strongest citation bursts. They indicated the research trend to some extent.

Figure 6

Co-cited references analysis indicated the research fronts and trend. (A) The timeline map of co-cited references. (B) Top 25 references with the strongest citation bursts. All results shown that the continuing hotspots in NTDs field included the understanding, preventing and proper treatment of NTDs.

Figure 7

GO enrichment analysis result. (A) GO functional classification. Red represents biological process level, green represents cellular component level, and blue represents molecular function level. (B) Top 25 of GO terms in the biological process (BP). (C) Top 25 of GO terms in the component (CC). (D) Top 25 of GO terms in the molecular function (MF).

Figure 8

KEGG enrichment analysis result. (A) Statistical charts of Grade B categories of each pathway. (B) Top 25 of KEGG enrichment pathways. (A,B) shown that NTDs-related genes were mainly enriched in pathways in cancer and signal transduction. (C) KEGG pathways network. The signals at the center of the top 25 signaling pathway interaction network include wnt, MAPK and PI3K-Akt signaling pathways.

Figure 9

SNP distribution and density map. (A) SNPs distribution map. It shown that there were 7 apparent SNPs clusters framed by red lines in chromosome 1, 3, 5, 11, 14, 17, and 21. SNPs indicated by arrows with frequency greater than 5 were colored by red or orange. (B) SNP density plot chromosome wise representing number of SNPs within 1 Mb window size. The horizontal axis shows the chromosome length (Mb); the different color depicts SNP density.