The temporal coordination of biological processes by the circadian clock is an important mechanism, and its disruption has negative health outcomes, including cancer. Experimental and theoretical ...evidence suggests that the oscillators driving the circadian clock and the cell cycle are coupled through phase locking.
We present a detailed and documented map of known mechanisms related to the regulation of the circadian clock, and its coupling with an existing cell cycle map which includes main interactions of the mammalian cell cycle. The coherence of the merged map has been validated with a qualitative dynamics analysis. We verified that the coupled circadian clock and cell cycle maps reproduce the observed sequence of phase markers. Moreover, we predicted mutations that contribute to regulating checkpoints of the two oscillators.
Our approach underlined the potential key role of the core clock protein NR1D1 in regulating cell cycle progression. We predicted that its activity influences negatively the progression of the cell cycle from phase G2 to M. This is consistent with the earlier experimental finding that pharmacological activation of NR1D1 inhibits tumour cell proliferation and shows that our approach can identify biologically relevant species in the context of large and complex networks.
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Abstract
Summary
The systems biology graphical notation (SBGN) has emerged as the main standard to represent biological maps graphically. It comprises three complementary languages: Process ...Description, for detailed biomolecular processes; Activity Flow, for influences of biological activities and Entity Relationship, for independent relations shared among biological entities. On the other hand, TikZ is one of the most commonly used package to ‘program’ graphics within TEX/LATEX. Here, we present sbgntikz, a TikZ library that allows drawing and customizing SBGN maps directly into TEX/LATEX documents, using the TikZ language. sbgntikz supports all glyphs of the three SBGN languages, and offers options that facilitate the drawing of complex glyph assembly within TikZ. Furthermore, sbgntikz is provided together with a converter that allows transforming any SBGN map stored under the SBGN Markup Language into a TikZ picture, or rendering it directly into a PDF file.
Availability and implementation
sbgntikz, the SBGN-ML to sbgntikz converter, as well as a complete documentation can be freely downloaded from https://github.com/Adrienrougny/sbgntikz/. The library and the converter are compatible with all recent operating systems, including Windows, MacOS, and all common Linux distributions.
Supplementary information
Supplementary material is available at Bioinformatics online.
Abstract
Summary
The systems biology graphical notation (SBGN) has emerged as the main standard to represent biological maps graphically. It comprises three complementary languages: Process ...Description, for detailed biomolecular processes; Activity Flow, for influences of biological activities and Entity Relationship, for independent relations shared among biological entities. On the other hand, TikZ is one of the most commonly used package to ‘program’ graphics within TEX/LATEX. Here, we present sbgntikz, a TikZ library that allows drawing and customizing SBGN maps directly into TEX/LATEX documents, using the TikZ language. sbgntikz supports all glyphs of the three SBGN languages, and offers options that facilitate the drawing of complex glyph assembly within TikZ. Furthermore, sbgntikz is provided together with a converter that allows transforming any SBGN map stored under the SBGN Markup Language into a TikZ picture, or rendering it directly into a PDF file.
Availability and implementation
sbgntikz, the SBGN-ML to sbgntikz converter, as well as a complete documentation can be freely downloaded from https://github.com/Adrienrougny/sbgntikz/. The library and the converter are compatible with all recent operating systems, including Windows, MacOS, and all common Linux distributions.
Supplementary information
Supplementary material is available at Bioinformatics online.
Burkholderia stabilis FERMP-21014 produces highly active cholesterol esterase in the presence of fatty acids. To develop an overexpression system for cholesterol esterase production, we carried out ...RNA sequencing analyses to screen strongly active promoters in FERMP-21014. Based on gene expression consistency analysis, we selected nine genes that were consistently expressed at high levels, following which we constructed expression vectors using their promoter sequences and achieved overproduction of extracellular cholesterol esterase under fatty acid-free conditions. Of the tested promoters, the promoter of BSFP_0720, which encodes the alkyl hydroperoxide reductase subunit AhpC, resulted in the highest cholesterol esterase activity (24.3 U mL
−1
). This activity level was 243-fold higher than that of the wild-type strain under fatty acid-free conditions. We confirmed that cholesterol esterase was secreted without excessive accumulation within the cells. The gene expression consistency analysis will be useful to screen promoters applicable to the overexpression of other industrially important enzymes.
Production of recombinant cholesterol esterase using consistently active promoters.
The Systems Biology Graphical Notation (SBGN) is an international community effort that aims to standardise the visualisation of pathways and networks for readers with diverse scientific backgrounds ...as well as to support an efficient and accurate exchange of biological knowledge between disparate research communities, industry, and other players in systems biology. SBGN comprises the three languages Entity Relationship, Activity Flow, and Process Description (PD) to cover biological and biochemical systems at distinct levels of detail. PD is closest to metabolic and regulatory pathways found in biological literature and textbooks. Its well-defined semantics offer a superior precision in expressing biological knowledge. PD represents mechanistic and temporal dependencies of biological interactions and transformations as a graph. Its different types of nodes include entity pools (e.g. metabolites, proteins, genes and complexes) and processes (e.g. reactions, associations and influences). The edges describe relationships between the nodes (e.g. consumption, production, stimulation and inhibition). This document details Level 1 Version 2.0 of the PD specification, including several improvements, in particular: 1) the addition of the equivalence operator, subunit, and annotation glyphs, 2) modification to the usage of submaps, and 3) updates to clarify the use of various glyphs (i.e. multimer, empty set, and state variable).
This document defines Version 0.3 Markup Language (ML) support for the Systems Biology Graphical Notation (SBGN), a set of three complementary visual languages developed for biochemists, modelers, ...and computer scientists. SBGN aims at representing networks of biochemical interactions in a standard, unambiguous way to foster efficient and accurate representation, visualization, storage, exchange, and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling. SBGN is defined neutrally to programming languages and software encoding; however, it is oriented primarily towards allowing models to be encoded using XML, the eXtensible Markup Language. The notable changes from the previous version include the addition of attributes for better specify metadata about maps, as well as support for multiple maps, sub-maps, colors, and annotations. These changes enable a more efficient exchange of data to other commonly used systems biology formats (e. g., BioPAX and SBML) and between tools supporting SBGN (e. g., CellDesigner, Newt, Krayon, SBGN-ED, STON, cd2sbgnml, and MINERVA). More details on SBGN and related software are available at
. With this effort, we hope to increase the adoption of SBGN in bioinformatics tools, ultimately enabling more researchers to visualize biological knowledge in a precise and unambiguous manner.
As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model ...disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.
Abstract
Summary
The systems biology graphical notation (SBGN) has become the de facto standard for the graphical representation of molecular maps. Having rapid and easy access to the content of ...large collections of maps is necessary to perform semantic or graph-based analysis of these resources. To this end, we propose StonPy, a new tool to store and query SBGN maps in a Neo4j graph database. StonPy notably includes a data model that takes into account all three SBGN languages and a completion module to automatically build valid SBGN maps from query results. StonPy is built as a library that can be integrated into other software and offers a command-line interface that allows users to easily perform all operations.
Availability and implementation
StonPy is implemented in Python 3 under a GPLv3 license. Its code and complete documentation are freely available from https://github.com/adrienrougny/stonpy.
Supplementary information
Supplementary data are available at Bioinformatics online.
Detailed maps of the molecular basis of the disease are powerful tools for interpreting data and building predictive models. Modularity and composability are considered necessary network features for ...large-scale collaborative efforts to build comprehensive molecular descriptions of disease mechanisms. An effective way to create and manage large systems is to compose multiple subsystems. Composable network components could effectively harness the contributions of many individuals and enable teams to seamlessly assemble many individual components into comprehensive maps. We examine manually built versions of the RAS-RAF-MEK-ERK cascade from the Atlas of Cancer Signalling Network, PANTHER and Reactome databases and review them in terms of their reusability and composability for assembling new disease models. We identify design principles for managing complex systems that could make it easier for investigators to share and reuse network components. We demonstrate the main challenges including incompatible levels of detail and ambiguous representation of complexes and highlight the need to address these challenges.
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A comprehensible representation of a molecular network is key to communicating and understanding scientific results in systems biology. The Systems Biology Graphical Notation (SBGN) has emerged as ...the main standard to represent such networks graphically. It has been implemented by different software tools, and is now largely used to communicate maps in scientific publications. However, learning the standard, and using it to build large maps, can be tedious. Moreover, SBGN maps are not grounded on a formal semantic layer and therefore do not enable formal analysis. Here, we introduce a new set of patterns representing recurring concepts encountered in molecular networks, called SBGN bricks. The bricks are structured in a new ontology, the Bricks Ontology (BKO), to define clear semantics for each of the biological concepts they represent. We show the usefulness of the bricks and BKO for both the template-based construction and the semantic annotation of molecular networks. The SBGN bricks and BKO can be freely explored and downloaded at sbgnbricks.org.
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