Deep learning from big data on cancer

International Symposium on Tumor Biology in Kanazawa & Symposium on Drug Discoverry in Academics 2014 [DATE]: January 23(Thu)-24(Fri),2014, [Place]:Kanazawa Excel Hotel Tpkyu, Kanazawa, Japan, [Organizers]:Kanazawa Association of Tumor Biologists / Cancer Research Institute, Kanazawa Universit

The gene regulatory system for specifying germ layers in early embryos of the simple chordate

動物胚の遺伝子発現を数式で表現 --動物の胚葉形成システムをまるごと理解--.京都大学プレスリリース. 2021-06-10.In animal embryos, gene regulatory networks control the dynamics of gene expression in cells and coordinate such dynamics among cells. In ascidian embryos, gene expression dynamics have been dissected at the single-cell resolution. Here, we revealed mathematical functions that represent the regulatory logics of all regulatory genes expressed at the 32-cell stage when the germ layers are largely specified. These functions collectively explain the entire mechanism by which gene expression dynamics are controlled coordinately in early embryos. We found that regulatory functions for genes expressed in each of the specific lineages contain a common core regulatory mechanism. Last, we showed that the expression of the regulatory genes became reproducible by calculation and controllable by experimental manipulations. Thus, these regulatory functions represent an architectural design for the germ layer specification of this chordate and provide a platform for simulations and experiments to understand the operating principles of gene regulatory networks

Gata is ubiquitously required for the earliest zygotic gene transcription in the ascidian embryo

In ascidian embryos, the earliest transcription from the zygotic genome begins between the 8-cell and 16-cell stages. Gata.a, a maternally expressed Gata transcription factor, activates target genes specifically in the animal hemisphere, whereas the complex of β-catenin and Tcf7 antagonizes the activity of Gata.a and activates target genes specifically in the vegetal hemisphere. Here, we show that genes zygotically expressed at the 16-cell stage have significantly more Gata motifs in their upstream regions. These genes included not only genes with animal hemisphere-specific expression but also genes with vegetal hemisphere-specific expression. On the basis of this finding, we performed knockdown experiments for Gata.a and reporter assays, and found that Gata.a is required for the expression of not only genes with animal hemisphere-specific expression, but also genes with vegetal hemisphere-specific expression. Our data indicated that weak Gata.a activity that cannot induce animal hemisphere-specific expression can allow β-catenin/Tcf7 targets to be expressed in the vegetal cells. Because genes zygotically expressed at the 32-cell stage also had significantly more Gata motifs in their upstream regions, Gata.a function may not be limited to the genes expressed specifically in the animal or vegetal hemispheres at the 16-cell stage, and Gata.a may play an important role in the earliest transcription of the zygotic genome

Using linkage logic theory to control dynamics of a gene regulatory network of a chordate embryo.

Linkage logic theory provides a mathematical criterion to control network dynamics by manipulating activities of a subset of network nodes, which are collectively called a feedback vertex set (FVS). Because many biological functions emerge from dynamics of biological networks, this theory provides a promising tool for controlling biological functions. By manipulating the activity of FVS molecules identified in a gene regulatory network (GRN) for fate specification of seven tissues in ascidian embryos, we previously succeeded in reproducing six of the seven cell types. Simultaneously, we discovered that the experimentally reconstituted GRN lacked information sufficient to reproduce muscle cells. Here, we utilized linkage logic theory as a tool to find missing edges in the GRN. Then, we identified a FVS from an updated version of the GRN and confirmed that manipulating the activity of this FVS was sufficient to induce all seven cell types, even in a multi-cellular environment. Thus, linkage logic theory provides tools to find missing edges in experimentally reconstituted networks, to determine whether reconstituted networks contain sufficient information to fulfil expected functions, and to reprogram cell fate

Controlling Cell Fate Specification System by Key Genes Determined from Network Structure

遺伝子ネットワークを制御してさまざまな種類の細胞を作り出す --数学的理論に基づく細胞運命の制御に成功--. 京都大学プレスリリース. 2018-06-13.Network structures describing regulation between biomolecules have been determined in many biological systems. Dynamics of molecular activities based on such networks are considered to be the origin of many biological functions. Recently, it has been proved mathematically that key nodes for controlling dynamics in networks are identified from network structure alone. Here, we applied this theory to a gene regulatory network for the cell fate specification of seven tissues in the ascidian embryo and found that this network, which consisted of 92 factors, had five key molecules. By controlling the activities of these key molecules, the specific gene expression of six of seven tissues observed in the embryo was successfully reproduced. Since this method is applicable to all nonlinear dynamic systems, we propose this method as a tool for controlling gene regulatory networks and reprogramming cell fates

RARGE: a large-scale database of RIKEN Arabidopsis resources ranging from transcriptome to phenome

The RIKEN Arabidopsis Genome Encyclopedia (RARGE) database houses information on biological resources ranging from transcriptome to phenome, including RIKEN Arabidopsis full-length (RAFL) complementary DNAs (cDNAs), their promoter regions, Dissociation (Ds) transposon-tagged lines and expression data from microarray experiments. RARGE provides tools for searching by resource code, sequence homology or keyword, and rapid access to detailed information on the resources. We have isolated 245 946 RAFL cDNA clones and collected 11 933 transposon-tagged lines, which are available from the RIKEN Bioresource Center and are stored in RARGE. The RARGE web interface can be accessed at http://rarge.gsc.riken.jp/. Additionally, we report 90 000 new RAFL cDNA clones here