Image Processing Research Team, RIKEN Center for Advanced Photonics (RAP)
ViBrism, a comprehensive gene expression database for the whole mouse brain
— Visualizing invisible biological processes using image processing technology —
The rapid advances in recent years in imaging using microscopes, CT scanning, and other technologies have led to a vast increase in both the quantity and diversity of image data. Team Leader Hideo Yokota has developed various image processing techniques to facilitate the discovery of principles of biological processes from image data and has made the resulting data publicly available. He spoke with us about the kind of databases he and his team are building, focusing in particular on ViBrism, which maps gene expression onto three-dimensional brain structure.
Hideo Yokota
Team Leader
Image Processing Research Team, RIKEN RAP
Extracting required information from increasingly multidimensional images
Image data generated by life science research is becoming increasingly multidimensional, ranging from 2D pixel images to 3D voxel images (arrays of tiny volume elements), and beyond to 4D and 5D with the addition of time and wavelength dimensions. The resulting volume of data is so vast that it no longer makes any sense to the naked eye.
This prompted us to develop an image information processing technology platform for facilitating the discovery of principles of life biological processes by, for example, enhancing definition to make the object under investigation easier to discern, and removing noise to highlight features. We have also built a cloud-based system, our 4D Cell Communication Platform, that enables the centralized management of multidimensional microscope images and their metadata. This resource can be accessed around the clock from within RIKEN for image management, processing, analysis, and sharing. In addition to basic research, we are working with the National Cancer Center Japan to develop highly accurate, machine learning-driven automated methods for detecting early-stage gastric cancer.
To go beyond simply observing images, we are also conducting research to generate shape models based on measurement data and conduct various simulations in virtual space. Running such simulations can further our understanding of the principles by which cells assume their various forms and perform their functions, as well as the metabolic reactions occurring within cells.
ViBrism, a database for comprehensively mapping gene expression in brain structure
ViBrism, one of the databases we have built and published, is a database that maps gene expression distribution in the whole mouse brain. The brain has a very complex structure closely related to function. The structure and functions of the brain are controlled by gene expression; it is our hope that shedding light on which genes are being expressed in each location within the brain will help to elucidate the mechanisms behind thinking and other brain functions, and to identify brain regions and genes that cause psychiatric and neurological diseases.
In collaboration with Professor Yuko Oho of Jissen Women’s University (at the time, a visiting researcher in RIKEN’s Bio-Research Infrastructure Construction Team), we developed a technique known as transcriptome tomography for reconstructing comprehensively measured gene expression information in three-dimensional space and investigated the distribution of gene expression in the whole mouse brain. Transcriptome tomography combines the use of a proprietary three-dimensional internal structure microscope (3D-ISM) with comprehensive analysis of gene expression using microarrays and other techniques (Fig. 1).
3D-ISM uses razor-sharp blades to slice specimens into cross sections about 10 microns thick, automatically scanning the section surfaces to generate image data as they repeatedly slice the specimen. Reconstructing the image data thereby obtained enables the brain’s outer shape and internal structure to be visualized in 3D on a computer, making it possible to observe any cross-section from any direction.
To elucidate gene expression patterns in 3D space, we prepare three samples that are sliced respectively in three planes: length, width, and height. We collect the resulting sections into batches called fractions, each of which is measured by microarray for amount of expression of approximately 36,000 genes. Reconstructing the results in 3D on a computer enables visualization of which genes are expressed at what level in each location in the brain. Using this technology, we created a map of the distribution of gene expression in the whole mouse brain and published it on ViBrism. The 3D information in ViBrism can also be analyzed in the same 3D space as MRI and other biological information.
Fig. 1: How transcriptome tomography works (top), and actual images illustrating the process (bottom)
(Top) Three samples are sliced in three orthogonal planes and gene expression density in each fraction is comprehensively measured by microarray. Based on the measured data, position in 3D space is estimated from the gene density of the fractions, and a gene expression map is reconstructed accordingly.
(Bottom) Measuring expression of the Slitrk6 gene in a mouse brain.
In typical conventional methods for creating gene expression maps, investigating expression patterns of individual genes in the brain requires as many samples as there are genes. With transcriptome tomography, however, only three samples are required to visualize comprehensive gene expression information in 3D space. Another advantage of transcriptome tomography is that measurement takes less than a month and costs approximately 5 million yen, which means it is much more efficient and less costly than conventional methods.
ViBrism enables the integrated analysis of multiple databases of spatial information and gene expression. Moving forward, we hope to expand our OLSP research to link with various other databases. I am also eager to probe the mysteries of the human brain by conducting a comprehensive analysis of gene expression in 3D space using the marmoset brain, which is closer to humans.
（Article by: Chisato Hata／Photo by: Tadashi Aizawa／Production assistance: Sci-Tech Communications)
Links
- Image Processing Research Team
- Research Project Data Link (in Japanese)
- ViBrism a comprehensive gene expression distribution map for the whole mouse brain
