title: Metadata Standard and Data Exchange Specifications to Describe, Model, and Integrate Complex and Diverse High-Throughput Screening Data from the Library of Integrated Network-based Cellular Signatures (LINCS).
abstract: The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource. Integration and analysis of diverse LINCS data sets depend on the availability of sufficient metadata to describe the assays and screening results and on their syntactic, structural, and semantic consistency. Here we report metadata specifications for the most important molecular and cellular components and recommend them for adoption beyond the LINCS project. We focus on the minimum required information to model LINCS assays and results based on a number of use cases, and we recommend controlled terminologies and ontologies to annotate assays with syntactic consistency and semantic integrity. We also report specifications for a simple annotation format (SAF) to describe assays and screening results based on our metadata specifications with explicit controlled vocabularies. SAF specifically serves to programmatically access and exchange LINCS data as a prerequisite for a distributed information management infrastructure. We applied the metadata specifications to annotate large numbers of LINCS cell lines, proteins, and small molecules. The resources generated and presented here are freely available.
authors: Center for Computational Science, University of Miami, Miami, FL, USA.
authors: Uma D
authors: UD
authors: Vempati
authors: Center for Computational Science, University of Miami, Miami, FL, USA.
authors: Caty
authors: C
authors: Chung
authors: Center for Computational Science, University of Miami, Miami, FL, USA.
authors: Chris
authors: C
authors: Mader
authors: Center for Computational Science, University of Miami, Miami, FL, USA.
authors: Amar
authors: A
authors: Koleti
authors: Center for Computational Science, University of Miami, Miami, FL, USA.
authors: Nakul
authors: N
authors: Datar
authors: Center for Computational Science, University of Miami, Miami, FL, USA.
authors: Dušica
authors: D
authors: Vidović
authors: ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, USA.
authors: David
authors: D
authors: Wrobel
authors: ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, USA.
authors: Sean
authors: S
authors: Erickson
authors: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Jeremy L
authors: JL
authors: Muhlich
authors: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Gabriel
authors: G
authors: Berriz
authors: Center for Molecular Therapeutics, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors: Cyril H
authors: CH
authors: Benes
authors: Broad Institute, Cambridge, Massachusetts, USA.
authors: Aravind
authors: A
authors: Subramanian
authors: National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland, USA.
authors: Ajay
authors: A
authors: Pillai
authors: ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA, USA Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Caroline E
authors: CE
authors: Shamu
authors: Center for Computational Science, University of Miami, Miami, FL, USA Department of Molecular and Cellular Pharmacology, University of Miami, Miami, Florida, USA sschurer@med.miami.edu.
authors: Stephan C
authors: SC
authors: Schürer
mesh_terms: D000906:Antibodies / Q000737:chemistry; D002460:Cell Line; D019295:Computational Biology / Q000379:methods*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D015723:Gene Library; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D020407:Internet; D007700:Kinetics; D008297:Male; D000071253:Metadata; D009154:Mutation; D009316:National Institutes of Health (U.S.); D010051:Ovarian Neoplasms / Q000378:metabolism; D011506:Proteins / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry; D014481:United States
chemical_list: D000906:Antibodies; D011506:Proteins; D034741:RNA, Small Interfering; D054852:Small Molecule Libraries
keywords: cell-based assays; data standards; database and data management; enzyme assays or enzyme kinetics; gene expression; metadata