Laboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain Science (CBS)
The Marmoset Gene Atlas:
A tool for understanding the human brain and determining the mechanisms of psychiatric/neurological illness
Marmosets have recently been in the spotlight as a new primate model. Team Leader Tomomi Shimogori has constructed and operates the Marmoset Gene Atlas. The Atlas also features a tool that can visualize gene expression patterns three-dimensionally to enable direct comparisons with human brain data, which is anticipated to lead to greater understanding of the human brain and determination of the mechanisms of psychiatric/neurological illness.
Tomomi Shimogori
Team Leader
Laboratory for Molecular Mechanisms of Brain Development, RIKEN CBS
Unit Leader
Neuroinformatics Unit, RIKEN CBS
Common marmosets have brains similar to those of humans and are well-suited for research
Determining the workings of the human brain and the causes of psychiatric/neurological illness at the molecular level require investigation of gene expression in the brain. However, due to ethical and technical problems, the brain cannot be examined via invasive methods in living humans. Although studies with mice have yielded a many findings, the human brain greatly differs, both structurally and functionally, from the murine brain; thus, there are limits to what can be learned from mouse research results.
Consequently, attention has recently focused on a small monkey called the common marmoset. Marmosets have brains with a structure resembling a human brain and exhibit a social nature similar to humans, such as living in families. In addition, they breed efficiently, their genes can be modified, and they are well-suited to research in other ways; as a result, they have begun to be used as a new animal model.
Searches from gene names, with results displayed in three dimensions
Japan was the first country in the world to successfully produce a genetically modified marmoset. This achievement has been leveraged with the Brain/MINDS project, begun in 2014 as a national project to comprehensively analyze the structure and functions of the marmoset brain. In this project, we have determined various gene expressions in the marmoset brain and published our findings in the Marmoset Gene Atlas (Fig. 1).
Fig. 1: Marmoset Gene Atlas website
https://gene-atlas.brainminds.jp/
As of March 2023, roughly 3000 gene samples have been registered in the Marmoset Gene Atlas. The site logs roughly 20,000 visits per year and is being increasingly cited in literature.
The Atlas allows users not only to look up where genes are expressed in the brain by name but also to search for expressed genes by brain region. Users can also look up where genes related to psychiatric/neurological illness are expressed in the brain. Thus, with applications from basic neurological research to clinical studies, the website can be utilized by a wide variety of researchers.
Since we analyze thin slices of brain, our gene expression data is two-dimensional. To compare this data with human MR (nuclear magnetic resonance) images, we must construct it in three dimensions. To do so, we worked with a researcher who specializes in image processing to develop “cerebral cortex gene expression projection mapping”, a tool that can visualize gene expression in the marmoset brain three-dimensionally. Since this tool enables viewing of multiple gene expression patterns in the brain from various angles simultaneously, comparisons with human brain data could aid in identifying which regions of the brain cause psychiatric/neurological illness.
Database integration and AI-driven future developments
Integration of the Marmoset Gene Atlas with other databases is likely to yield further developments going forward. For example, inputting a gene name could allow users to search for expression patterns in mice and other laboratory animals and bring up displays of information on diseases associated with that gene and human MR images of brain regions where that gene is expressed. In ways such as these, we envision developing a system that permits cross-cutting searches of data in multiple dimensions.
In addition, similar to online shopping websites displaying other items you may be interested in, we envision introducing a function that displays related information. For example, say that a researcher specializing in diseases in a certain organ is looking at genes associated with that disease in another database. If the database tells the researcher, “This gene is expressed in this region of the brain, which has this function”, they may think, “Maybe this disease is associated with this brain function” or gain some other suggestion that had never occurred to them before, thereby expanding their research. Database integration could be a game-changer that goes beyond the barriers between specialized fields and thus accelerate research. At the OLSP, we are starting to consider integrating other RIKEN databases.
Personnel and budget support are essential for maintaining and developing databases
Maintaining and further developing databases requires not only collaboration with researchers in AI and image processing, but also support for budgets and personnel development. The Marmoset Gene Atlas was established nearly 10 years ago and, in that time, has grown into a database used by researchers around the world. Going forward, we hope to obtain support for maintaining and developing the Atlas, make it more valuable, and thereby contribute to the development of science.
(Article by: Chisato Hata／Production assistance: Sci-Tech Communications)
