Masaomi Nishimura

Transcriptome Tomography for Brain Analysis in the Web-Accessible Anatomical Space

Increased information on the encoded mammalian genome is expected to facilitate an integrated understanding of complex anatomical structure and function based on the knowledge of gene products. Determination of gene expression-anatomy associations is crucial for this understanding. To elicit the association in the three-dimensional (3D) space, we introduce a novel technique for comprehensive mapping of endogenous gene expression into a web-accessible standard space: Transcriptome Tomography. The technique is based on conjugation of sequential tissue-block sectioning, all fractions of which are used for molecular measurements of gene expression densities, and the block- face imaging, which are used for 3D reconstruction of the fractions. To generate a 3D map, tissues are serially sectioned in each of three orthogonal planes and the expression density data are mapped using a tomographic technique. This rapid and unbiased mapping technique using a relatively small number of original data points allows researchers to create their own expression maps in the broad anatomical context of the space. In the first instance we generated a dataset of 36,000 maps, reconstructed from data of 61 fractions measured with microarray, covering the whole mouse brain (ViBrism: http://vibrism.riken.jp/3dviewer/ex/index.html) in one month. After computational estimation of the mapping accuracy we validated the dataset against existing data with respect to the expression location and density. To demonstrate the relevance of the framework, we showed disease related expression of Huntington’s disease gene and Bdnf. Our tomographic approach is applicable to analysis of any biological molecules derived from frozen tissues, organs and whole embryos, and the maps are spatially isotropic and well suited to the analysis in the standard space (e.g. Waxholm Space for brain-atlas databases). This will facilitate research creating and using open-standards for a molecular-based understanding of complex structures; and will contribute to new insights into a broad range of biological and medical questions.

Conformational plasticity of JRAB/MICAL-L2 provides “law and order” in collective cell migration

A multidisciplinary approach reveals key insights into the principles of collective cell migration, which is involved in fundamental biological processes. The conformational plasticity of a single molecule, JRAB/MICAL-L2, provides “law and order” in collective cell migration.

Broad Integration of Expression Maps and Co-Expression Networks Compassing Novel Gene Functions in the Brain

Using a recently invented technique for gene expression mapping in the whole-anatomy context, termed transcriptome tomography, we have generated a dataset of 36,000 maps of overall gene expression in the adult-mouse brain. Here, using an informatics approach, we identified a broad co-expression network that follows an inverse power law and is rich in functional interaction and gene-ontology terms. Our framework for the integrated analysis of expression maps and graphs of co-expression networks revealed that groups of combinatorially expressed genes, which regulate cell differentiation during development, were present in the adult brain and each of these groups was associated with a discrete cell types. These groups included non-coding genes of unknown function. We found that these genes specifically linked developmentally conserved groups in the network. A previously unrecognized robust expression pattern covering the whole brain was related to the molecular anatomy of key biological processes occurring in particular areas.

Biomedical Image Communication Platform

Recent progress in the field of biomedical imaging has led to the demand for large-scale three-dimensional (3D) image analysis in modern biology. Existing image-processing systems lack either cloud computing services or advanced 3D processing ability. This paper proposes a novel cloud-based communication platform for biomedical images. The system provides visualization, data management, and image-processing functions through a standard web browser. Therefore, the sharing of limited software and hardware resources is achieved, allowing for effective collaboration between researchers. We demonstrate the applicability and functionality of the system by examining typical case studies on biomedical images.

A statistical image analysis framework for pore-free islands derived from heterogeneity distribution of nuclear pore complexes

Nuclear pore complexes (NPCs) maintain cellular homeostasis by mediating nucleocytoplasmic transport. Although cyclin-dependent kinases (CDKs) regulate NPC assembly in interphase, the location of NPC assembly on the nuclear envelope is not clear. CDKs also regulate the disappearance of pore-free islands, which are nuclear envelope subdomains; this subdomain gradually disappears with increase in homogeneity of the NPC in response to CDK activity. However, a causal relationship between pore-free islands and NPC assembly remains unclear. Here, we elucidated mechanisms underlying NPC assembly from a new perspective by focusing on pore-free islands. We proposed a novel framework for image-based analysis to automatically determine the detailed ‘landscape’ of pore-free islands from a large quantity of images, leading to the identification of NPC intermediates that appear in pore-free islands with increased frequency in response to CDK activity. Comparison of the spatial distribution between simulated and the observed NPC intermediates within pore-free islands showed that their distribution was spatially biased. These results suggested that the disappearance of pore-free islands is highly related to de novo NPC assembly and indicated the existence of specific regulatory mechanisms for the spatial arrangement of NPC assembly on nuclear envelopes.

Construction of Integrated Mechanical Simulation Model of Whole Body for Alive Human

We are aiming at the mechanical simulation intended for the human body. The targeted mechanical simulation is structural mechanics (bone and soft tissue), fluid dynamics (blood flow), and kinetic (movement of the body). It constructs the simulation model of the whole body that can unitedly do these analyses. Moreover, it includes shape and the mechanical property in this model for the human body to be alive. We took a picture of X-ray CT and MRI for the volunteer. It created the data of 1mm voxel based on information of which it took a picture by X-ray CT. It can identify the soft tissue from the data of MRI. However, it has the spatial resolution and the problem of the distortion of the space, and it cannot construct the model as it is. We matched information on Xray CT and MRI, and constructed the whole body model. In addition, it can request the Young’s modulus of the bone in the measurement of the mechanical property value according to the X-ray transmission rate. We developed the automated system by which it requested the shape of the whole body and the Young’s modulus of the bone from transmission factor of X-ray CT. We had developed system was able to create VCAD data of the whole body of the human body. VCAD system is an integrated system of CAD,CAM,CAE. In this human body model we can manufacture the structure analysis, the flow analysis, and the implant constructed.