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1.
Cell ; 171(6): 1437-1452.e17, 2017 Nov 30.
Article in English | MEDLINE | ID: mdl-29195078

ABSTRACT

We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs, and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io.


Subject(s)
Gene Expression Profiling/methods , Cell Line, Tumor , Drug Resistance, Neoplasm , Gene Expression Profiling/economics , Humans , Neoplasms/drug therapy , Organ Specificity , Pharmaceutical Preparations/metabolism , Sequence Analysis, RNA/economics , Sequence Analysis, RNA/methods , Small Molecule Libraries
2.
Nucleic Acids Res ; 40(Database issue): D700-5, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22110037

ABSTRACT

The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use.


Subject(s)
Databases, Genetic , Genome, Fungal , Saccharomyces cerevisiae/genetics , Genes, Fungal , Genomics , High-Throughput Nucleotide Sequencing , Molecular Sequence Annotation , Phenotype , Software , Terminology as Topic
3.
Nucleic Acids Res ; 38(Database issue): D433-6, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19906697

ABSTRACT

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is a scientific database for the molecular biology and genetics of the yeast Saccharomyces cerevisiae, which is commonly known as baker's or budding yeast. The information in SGD includes functional annotations, mapping and sequence information, protein domains and structure, expression data, mutant phenotypes, physical and genetic interactions and the primary literature from which these data are derived. Here we describe how published phenotypes and genetic interaction data are annotated and displayed in SGD.


Subject(s)
Computational Biology/methods , Databases, Nucleic Acid , Genome, Fungal , Mutation , Saccharomyces cerevisiae/genetics , Computational Biology/trends , DNA, Fungal , Databases, Genetic , Databases, Protein , Genes, Fungal , Information Storage and Retrieval/methods , Internet , Phenotype , Protein Structure, Tertiary , Software
4.
Nucleic Acids Res ; 36(Database issue): D577-81, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17982175

ABSTRACT

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) collects and organizes biological information about the chromosomal features and gene products of the budding yeast Saccharomyces cerevisiae. Although published data from traditional experimental methods are the primary sources of evidence supporting Gene Ontology (GO) annotations for a gene product, high-throughput experiments and computational predictions can also provide valuable insights in the absence of an extensive body of literature. Therefore, GO annotations available at SGD now include high-throughput data as well as computational predictions provided by the GO Annotation Project (GOA UniProt; http://www.ebi.ac.uk/GOA/). Because the annotation method used to assign GO annotations varies by data source, GO resources at SGD have been modified to distinguish data sources and annotation methods. In addition to providing information for genes that have not been experimentally characterized, GO annotations from independent sources can be compared to those made by SGD to help keep the literature-based GO annotations current.


Subject(s)
Databases, Genetic , Genes, Fungal , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Computational Biology , Genome, Fungal , Genomics , Internet , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/physiology , User-Computer Interface , Vocabulary, Controlled
5.
Nucleic Acids Res ; 35(Database issue): D468-71, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17142221

ABSTRACT

The recent explosion in protein data generated from both directed small-scale studies and large-scale proteomics efforts has greatly expanded the quantity of available protein information and has prompted the Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) to enhance the depth and accessibility of protein annotations. In particular, we have expanded ongoing efforts to improve the integration of experimental information and sequence-based predictions and have redesigned the protein information web pages. A key feature of this redesign is the development of a GBrowse-derived interactive Proteome Browser customized to improve the visualization of sequence-based protein information. This Proteome Browser has enabled SGD to unify the display of hidden Markov model (HMM) domains, protein family HMMs, motifs, transmembrane regions, signal peptides, hydropathy plots and profile hits using several popular prediction algorithms. In addition, a physico-chemical properties page has been introduced to provide easy access to basic protein information. Improvements to the layout of the Protein Information page and integration of the Proteome Browser will facilitate the ongoing expansion of sequence-specific experimental information captured in SGD, including post-translational modifications and other user-defined annotations. Finally, SGD continues to improve upon the availability of genetic and physical interaction data in an ongoing collaboration with BioGRID by providing direct access to more than 82,000 manually-curated interactions.


Subject(s)
Databases, Protein , Proteomics , Saccharomyces cerevisiae Proteins/chemistry , Computer Graphics , Genome, Fungal , Internet , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Sequence Analysis, Protein , User-Computer Interface
6.
Nucleic Acids Res ; 34(Database issue): D442-5, 2006 Jan 01.
Article in English | MEDLINE | ID: mdl-16381907

ABSTRACT

Sequencing and annotation of the entire Saccharomyces cerevisiae genome has made it possible to gain a genome-wide perspective on yeast genes and gene products. To make this information available on an ongoing basis, the Saccharomyces Genome Database (SGD) (http://www.yeastgenome.org/) has created the Genome Snapshot (http://db.yeastgenome.org/cgi-bin/genomeSnapShot.pl). The Genome Snapshot summarizes the current state of knowledge about the genes and chromosomal features of S.cerevisiae. The information is organized into two categories: (i) number of each type of chromosomal feature annotated in the genome and (ii) number and distribution of genes annotated to Gene Ontology terms. Detailed lists are accessible through SGD's Advanced Search tool (http://db.yeastgenome.org/cgi-bin/search/featureSearch), and all the data presented on this page are available from the SGD ftp site (ftp://ftp.yeastgenome.org/yeast/).


Subject(s)
Databases, Genetic , Genome, Fungal , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Chromosomes, Fungal , Computer Graphics , Genomics , Internet , Saccharomyces cerevisiae Proteins/classification , Saccharomyces cerevisiae Proteins/physiology , User-Computer Interface
7.
Nucleic Acids Res ; 33(Database issue): D374-7, 2005 Jan 01.
Article in English | MEDLINE | ID: mdl-15608219

ABSTRACT

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) is a scientific database of gene, protein and genomic information for the yeast Saccharomyces cerevisiae. SGD has recently developed two new resources that facilitate nucleotide and protein sequence comparisons between S.cerevisiae and other organisms. The Fungal BLAST tool provides directed searches against all fungal nucleotide and protein sequences available from GenBank, divided into categories according to organism, status of completeness and annotation, and source. The Model Organism BLASTP Best Hits resource displays, for each S.cerevisiae protein, the single most similar protein from several model organisms and presents links to the database pages of those proteins, facilitating access to curated information about potential orthologs of yeast proteins.


Subject(s)
Databases, Genetic , Genome, Fungal , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Software , Saccharomyces cerevisiae Proteins/chemistry , Sequence Analysis
8.
Nucleic Acids Res ; 32(Database issue): D311-4, 2004 Jan 01.
Article in English | MEDLINE | ID: mdl-14681421

ABSTRACT

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/), a scientific database of the molecular biology and genetics of the yeast Saccharomyces cerevisiae, has recently developed several new resources that allow the comparison and integration of information on a genome-wide scale, enabling the user not only to find detailed information about individual genes, but also to make connections across groups of genes with common features and across different species. The Fungal Alignment Viewer displays alignments of sequences from multiple fungal genomes, while the Sequence Similarity Query tool displays PSI-BLAST alignments of each S.cerevisiae protein with similar proteins from any species whose sequences are contained in the non-redundant (nr) protein data set at NCBI. The Yeast Biochemical Pathways tool integrates groups of genes by their common roles in metabolism and displays the metabolic pathways in a graphical form. Finally, the Find Chromosomal Features search interface provides a versatile tool for querying multiple types of information in SGD.


Subject(s)
Computational Biology , Databases, Genetic , Genome, Fungal , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Amino Acid Sequence , Animals , Humans , Information Storage and Retrieval , Internet , Molecular Sequence Data , Saccharomyces cerevisiae Proteins/chemistry , Sequence Alignment , Sequence Homology , Software
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