Meta-Research: Understudied genes are lost in a leaky pipeline between genome-wide assays and reporting of results.

ABSTRACT

Present-day publications on human genes primarily feature genes that already appeared in many publications prior to completion of the Human Genome Project in 2003. These patterns persist despite the subsequent adoption of high-throughput technologies, which routinely identify novel genes associated with biological processes and disease. Although several hypotheses for bias in the selection of genes as research targets have been proposed, their explanatory powers have not yet been compared. Our analysis suggests that understudied genes are systematically abandoned in favor of better-studied genes between the completion of -omics experiments and the reporting of results. Understudied genes remain abandoned by studies that cite these -omics experiments. Conversely, we find that publications on understudied genes may even accrue a greater number of citations. Among 45 biological and experimental factors previously proposed to affect which genes are being studied, we find that 33 are significantly associated with the choice of hit genes presented in titles and abstracts of -omics studies. To promote the investigation of understudied genes, we condense our insights into a tool, find my understudied genes (FMUG), that allows scientists to engage with potential bias during the selection of hits. We demonstrate the utility of FMUG through the identification of genes that remain understudied in vertebrate aging. FMUG is developed in Flutter and is available for download at fmug.amaral.northwestern.edu as a MacOS/Windows app.

Modern techniques for studying human genetics have helped to identify 20,000 protein-encoding genes in the human genome. Yet scientists have not studied most of them, including genes linked to human diseases in genome wide studies. For example, about 44% of the genes associated with Alzheimer's disease have never been mentioned in the title or summary of a scientific article. Why so many health-linked genes have yet to be examined is unclear. Many genetic studies instead focus on genes already studied before the Human Genome Project mapped the entire genome in 2003. There are many reasons why scientists may ignore potentially disease-causing genes. They may feel that well-studied genes are safer bets or more likely to result in high-profile publications. Or they may lack the tools to study less well-characterized genes. Richardson et al. analyzed the scientific literature for clues on why so many genes are being ignored by scientists. The analysis included hundreds of articles that used a wide range of genetic techniques, including genome-wide association studies, RNA sequencing, and gene editing tools to scour the genome for disease-linked genes. It revealed that scientists abandon the study of many genes early in the research process and identify 33 reasons why. Contrary to scientists' fears, Richardson et al. show that reports on understudied genes often garner more attention than studies on well-known genes. Richardson et al. used their results to create a downloadable tool called "Find My Understudied Genes (FMUG)" to help scientists identify understudied genes and counteract bias toward more well-studied genes. The app may help scientists make informed decisions about which understudied genes to research. If the tool helps boost investigation of understudied genes, it may help speed up progress towards understanding human genetics and how various genes may contribute to diseases.