ABSTRACT
The development of effective vaccines in <1 year to combat the spread of coronavirus disease 19 (COVID-19) is an example of particularly rapid progress in biomedicine. However, this was only made possible by decades of investment in scientific research. Many important research commentaries and reviews have been provided to describe the various contributions and scientific breakthroughs that led to the development of COVID-19 vaccines. In this work, we sought to complement those efforts by adding a systematic and quantitative study of the research foundations that led to these vaccines. Here, we analyzed citations from COVID-19 vaccine research articles to determine which scientific areas of study contributed the most to this research. Our findings revealed that coronavirus research was cited most often, and by a large margin. However, significant contributions were also seen from a diverse set of fields such as cancer, diabetes, and HIV/AIDS. In addition, we examined the publication history of the most prolific authors of COVID-19 vaccine research to determine their research expertise prior to the pandemic. Interestingly, although COVID-19 vaccine research relied most heavily on previous coronavirus work, we find that the most prolific authors on these publications most often had expertise in other areas including influenza, cancer, and HIV/AIDS. Finally, we used machine learning to identify and group together publications based on their major topic areas. This allowed us to elucidate the differences in citations between research areas. These findings highlight and quantify the relevance of prior research from a variety of scientific fields to the rapid development of a COVID-19 vaccine. This study also illustrates the importance of funding and sustaining a diverse research enterprise to facilitate a rapid response to future pandemics.
ABSTRACT
Human linkage and association studies suggest a gene(s) for nonsyndromic cleft lip with or without cleft palate (CL/P) on chromosome 4q31-q32 at or near the platelet-derived growth factor-C (PDGF-C) locus. The mouse Pdgfc(-/-) knockout shows that PDGF-C is essential for palatogenesis. To evaluate the role of PDGF-C in human clefting, we performed sequence analysis and SNP genotyping using 1048 multiplex CL/P families and 1000 case-control samples from multiple geographic origins. No coding region mutations were identified, but a novel -986 C>T SNP (rs28999109) was significantly associated with CL/P (P=0.01) in cases from Chinese families yielding evidence of linkage to 4q31-q32. Significant or near-significant association was also seen for this and several other PDGF-C SNPs in families from the United States, Spain, India, Turkey, China, and Colombia, whereas no association was seen in families from the Philippines, and Guatemala, and case-controls from Brazil. The -986T allele abolished six overlapping potential transcription regulatory motifs. Transfection assays of PDGF-C promoter reporter constructs show that the -986T allele is associated with a significant decrease (up to 80%) of PDGF-C gene promoter activity. This functional polymorphism acting on a susceptible genetic background may represent a component of human CL/P etiology.
