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Functional Metabolomics Describes the Yeast Biosynthetic Regulome.

Cell | 2016

Genome-metabolism interactions enable cell growth. To probe the extent of these interactions and delineate their functional contributions, we quantified the Saccharomyces amino acid metabolome and its response to systematic gene deletion. Over one-third of coding genes, in particular those important for chromatin dynamics, translation, and transport, contribute to biosynthetic metabolism. Specific amino acid signatures characterize genes of similar function. This enabled us to exploit functional metabolomics to connect metabolic regulators to their effectors, as exemplified by TORC1, whose inhibition in exponentially growing cells is shown to match an interruption in endomembrane transport. Providing orthogonal information compared to physical and genetic interaction networks, metabolomic signatures cluster more than half of the so far uncharacterized yeast genes and provide functional annotation for them. A major part of coding genes is therefore participating in gene-metabolism interactions that expose the metabolism regulatory network and enable access to an underexplored space in gene function.

Pubmed ID: 27693354 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


SGD (tool)

RRID:SCR_004694

A curated database that provides comprehensive integrated biological information for Saccharomyces cerevisiae along with search and analysis tools to explore these data. SGD allows researchers to discover functional relationships between sequence and gene products in fungi and higher organisms. The SGD also maintains the S. cerevisiae Gene Name Registry, a complete list of all gene names used in S. cerevisiae which includes a set of general guidelines to gene naming. Protein Page provides basic protein information calculated from the predicted sequence and contains links to a variety of secondary structure and tertiary structure resources. Yeast Biochemical Pathways allows users to view and search for biochemical reactions and pathways that occur in S. cerevisiae as well as map expression data onto the biochemical pathways. Literature citations are provided where available.

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Yeast Search for Transcriptional Regulators And Consensus Tracking (tool)

RRID:SCR_006076

A curated repository of more than 206000 regulatory associations between transcription factors (TF) and target genes in Saccharomyces cerevisiae, based on more than 1300 bibliographic references. It also includes the description of 326 specific DNA binding sites shared among 113 characterized TFs. Further information about each Yeast gene has been extracted from the Saccharomyces Genome Database (SGD). For each gene the associated Gene Ontology (GO) terms and their hierarchy in GO was obtained from the GO consortium. Currently, YEASTRACT maintains a total of 7130 terms from GO. The nucleotide sequences of the promoter and coding regions for Yeast genes were obtained from Regulatory Sequence Analysis Tools (RSAT). All the information in YEASTRACT is updated regularly to match the latest data from SGD, GO consortium, RSA Tools and recent literature on yeast regulatory networks. YEASTRACT includes DISCOVERER, a set of tools that can be used to identify complex motifs found to be over-represented in the promoter regions of co-regulated genes. DISCOVERER is based on the MUSA algorithm. These algorithms take as input a list of genes and identify over-represented motifs, which can then be compared with transcription factor binding sites described in the YEASTRACT database.

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YeTFaSCo (tool)

RRID:SCR_006893

Collection of all available transcription factor (TF) specificities for the yeast Saccharomyces cerevisiae in Position Frequency Matrix (PFM) or Position Weight Matrix (PWM) formats. The specificities are evaluated for quality using several metrics. With this website, you can scan sequences with the motifs to find where potential binding sites lie, inspect precomputed genome-wide binding sites, find which TFs have similar motifs to one you have found, and download the collection of motifs. Submissions are welcome.

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Biological General Repository for Interaction Datasets (BioGRID) (tool)

RRID:SCR_007393

Curated protein-protein and genetic interaction repository of raw protein and genetic interactions from major model organism species, with data compiled through comprehensive curation efforts.

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GE Healthcare (tool)

RRID:SCR_000004

A commercial antibody supplier and provider of various services.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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PubMed (tool)

RRID:SCR_004846

Public bibliographic database that provides access to citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. PubMed citations and abstracts include fields of biomedicine and health, covering portions of life sciences, behavioral sciences, chemical sciences, and bioengineering. Provides access to additional relevant web sites and links to other NCBI molecular biology resources. Publishers of journals can submit their citations to NCBI and then provide access to full-text of articles at journal web sites using LinkOut.

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Cold Spring Harbor Laboratory (tool)

RRID:SCR_008326

Non profit, private research and education institution that performs molecular and genetic research used to generate methods for better diagnostics and treatments for cancer and neurological diseases. Research of cancer causing genes and their respective signaling pathways, mutations and structural variations of the human genome that could cause neurodevelopmental and neurodegenerative illnesses such as autism, schizophrenia, and Alzheimer's and Parkinson's diseases and also research in plant genetics and quantitative biology.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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Mendeley Data (tool)

RRID:SCR_002750

A free reference manager and academic social network to organize your research, collaborate with others online, and discover the latest research. Automatically generate bibliographies, Collaborate easily with other researchers online, Easily import papers from other research software, Find relevant papers based on what you're reading, Access your papers from anywhere online, Read papers on the go with the iPhone app. The software, Mendeley Desktop, offers: * Automatic extraction of document details * Efficient management of your papers * Sharing and synchronization of your library (or parts of it) * Additional features: A plug-in for citing your articles in Microsoft Word, OCR (image-to-text conversion, so you can full-text search all your scanned PDFs), etc The website, Mendeley Web, complements Mendeley Desktop by offering these features: * An online back up of your library * Statistics of all things interesting * A research network that allows you to keep track of your colleagues' publications, conference participations, awards etc * A recommendation engine for papers that might interest you

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GOstat (tool)

RRID:SCR_008535

GOstat is a tool that allows you to find statistically overrepresented Gene Ontologies within a group of genes. The Gene-Ontology database (GO: http://www.geneontology.org) provides a useful tool to annotate and analyze the function of large numbers of genes. Modern experimental techniques, as e.g. DNA microarrays, often result in long lists of genes. To learn about the biology in this kind of data it is desirable to find functional annotation or Gene-Ontology groups which are highly represented in the data. This program (GOstat) should help in the analysis of such lists and will provide statistics about the GO terms contained in the data and sort the GO annotations giving the most representative GO terms first. Run GOstat: * Go to search form - Computes GO statistics of a list of genes selected from a microarray. * GOstat Display - You can store results from a previously run and view them here, either by uploading them as a file or putting them on a selected URL. * Upload Custom GO Annotations - This allows you to upload your own GO annotation database and use it with GOstat. Variants of GOstat: * Rank GOstat - Takes input from all genes on microarray instead of using a fixed cutoff and uses ranks using a Wilcoxon test or either ranks or pvalues to score GOs using Kolmogorov-Smirnov statistics. * Gene Abundance GOstats - Takes input from all genes on microarray and sums up the gene abundances for each GO to compute statistics. * Two list GOstat - Compares GO statistics in two independent lists of genes, not necessarily one of them being the complete list the other list is sampled from. Platform: Online tool

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MetaboLights (tool)

RRID:SCR_014663

A cross-species, cross-technique database for metabolomics experiments, data, and derived information. It includes metabolite structures and their reference spectra, their biological roles, locations and concentrations, and experimental data from metabolic experiments.

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STRING (tool)

RRID:SCR_005223

Database of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)

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Goat Anti-Mouse IgG (H L)-HRP Conjugate (antibody)

RRID:AB_11125547

This unknown targets Goat Mouse IgG (H L)-HRP Conjugate

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GFP (antibody)

RRID:AB_2313768

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GFP-avictoria (antibody)

RRID:AB_303395

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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Goat Anti-Mouse IgG (H L)-HRP Conjugate (antibody)

RRID:AB_11125547

This unknown targets Goat Mouse IgG (H L)-HRP Conjugate

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GFP (antibody)

RRID:AB_2313768

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