cebs database: a structure for data integration across studies 26 june 2013
TRANSCRIPT
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CEBS Database: a structure for data integration across studies
26 June 2013
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Chemical Effects in Biological Systems (CEBS)
• Relational public database
– User interface
– FTP site with data domain “bundles”
• Private database + file system (Bins)
• Owner is the US National Toxicology Program. Committed to the use of CEBS to store and serve to the public data from NTP studies.
• CEBS: http://cebs.niehs.nih.gov
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Example 1
• See all studies in CEBS related to a test article (Toluene)
• How studies are organized in CEBS
• How to access study-level data
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www.cebs.niehs.nih.gov
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CEBS Home Page
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Select Test Article
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Investigations using that Test Article
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2-year rat study
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Design tab – explains the groups and the comparators
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Timeline Tab – gives the study events and protocols
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Timeline Tab – gives the study events and protocols
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Study data by “domains”
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Study data by “domains”
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Example 2
• Find data for male rats with liver injury
• Example of searching across studies using CEBS
– Search using pathology results, also get all data from these animals
• Example of limitations of data in CEBS
– Legacy NTP terminology
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Searching across studies
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The CEBS Workspace
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Details for studies in selected list
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The CEBS Workspace
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Chemicals in selected studies
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The CEBS Workspace
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All data are collected
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Quick review of clinical chemistry…..
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Example 3
• Visual datamining over all data in a domain
• This workflow is implemented for Tox21 phase 1 data
– 1408 compounds
– 117 assays
• The Tox21 phase I data was just made public, and this change has not yet been implemented in CEBS
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Select assay -- or -- Select chemical
View responsein context ofall assays andall chemicals
Select theresponse levelof interest
Combine searches
Download
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Responses of all assays to all chemicals; target assay is highlighted
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Clustered bi-directionally to group assays and chemicals on the basis of response
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Additional functionality: look up chemical or assay.
Click to get “cursor”To highlight assay of interest
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After reviewing responses select response level(s) of interest:
Get list of chemicals producing that response:
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Look up chemical to find the assays with response of selected level(s):
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Examples
• Example 1
– Data for an individual study
– CEBS standard and user-defined report formats
• Example 2
– Cross-study query
– Use of My Workspace to review aspects of query results
• Example 3
– Cross-domain review of results
– Selection of responsive assays or responsive chemicals
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How is CEBS organized?
• Meta data
– Biological context, design, protocol and participant information
• Data
– Based on assays (on specimen)
– Or observations made during in-life phase
• Database organization
– Study description and Assay domains
• Data format for loading
– SIFT: Simple Investigation Formatted Text
• CEBS Data Dictionary
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TIME
Biological context:
Take specimens: liver, blood, kidney, for histopathology and microarray
Treatment: 0, 50, 150, 1500 mg/kg Acetaminophen by gavage 5 male Sprague-Dawley rats per group
In life observations: in-cage morbidity, behavior
Care: feed, housingtime of day of dosing
Sacrifice: using anesthesia, time of day
24 486
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TIME
Study design: groups, comparators, and study factors
24 486
0
50
150
1500
Time-matchedcomparators
6-0
6-50
6-150
6-1500
24-0
24-50
24-150
24-1500
48-0
48-50
48-150
48-1500
DO
SE
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CEBS database design
Original dataIn file system
Protocols
Timeline
Study meta-data
GroupsSubjects
Participant Characteristics
AssayInput
Fold Changes
Trial /trend results
Activity calls
Conclusions
HistopathologyClinical PathologyGenetic ToxicologyImmunotoxicology
PCR
Microarray
Tox21
Study data
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SIFT: Standard format for loading CEBS
• Simple Investigation Formatted Text
• Syntax based on SOFT (GEO; www.ncbi.nlm.nih.gov/geo/)
• Used to capture
– Study meta-data
– Study data
– Data transformation
• Tools (java)
– SIFT Loader (loads CEBS)
– SIFT validator
– CEBS SIFTBuilder
• Uses CEBS data dictionary to validate
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Other Toxicogenomics DatabaseMIAME/Tox & Tox/ArrayExpress HESI Committee: Application of Genomics
to Mechanism based Risk Assessment US National Center for Toxicogenomics The EMBL European Bioinformatics Institute
Formats for Exchange of Toxicity Data with RegulatorsSEND Standard for Exchange of Nonclinical Data
CDISC, Pharmquest
21CFR part11-compliant repositories, e.g. Tox/Path from Xybion Medical SystemsData
Dictionary
Repositories for Toxicity DataIn Vivo Data Warehouse Lilly Greenfield Research LabsTDMS and ClinChem DB US National Toxicity Program
LIMS systems MAPS (NIEHS) TSP (US EPA)
Toxicity Data Indexed by Chemical Structure
DSSTox, US EPAToxML, LIST Consortium
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CEBS DD: toxicological terms and synonyms from various sources
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CEBS DD evolution
• Started in 2003
• Originally text based, now XML
• Based on definition tables in CEBS
• Correlation with other syntaxes used to build parsers for various data formats
• Currently aligned with
– SEND (Standards for Exchange of Nonclinical Data)
– OBI (Ontology for Biomedical Investigations
• SIFT uses original MAGE-Tab for microarray data
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Curation
• Pipelines
– The CEBS team has four human curators who verify that studies have biologically sensible information in the CEBS presentation screen.
• Individual studies
– If an individual provides a study for depositon into CEBS, that person is requested to visually confirm that the study presents correctly
• Loads from NTP databases
– Automated scripts compare the number of studies, observations, subjects, etc.
• Term consolidation
– Woroking with pathologists and ontologist
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Towards Linked Data
Participant characteristics (meta data)
Histopathology observations (data)
Start with SIFT Tabular Data (implicit relationships)
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…convert to RDF triples with explicit relationships in the data
:group1-cage1-1 rdfs:label "GROUP1_CAGE1_1" ; # This subject rdf:type obo:NCBITaxon_10090 ; # is a mouse sift:member-of :group1-cage1 ; # member of sub-group :group1-cage1 bfo:0000159 obo:PATO_0000384 ; # has quality at all times: male sift:dose :dose-0 ; # has dose :dose-0 sift:death-status :terminal-sacrifice ; # was sacrificed sift:death-date :study-day-731 . # died on day 731
:group1-cage1-1-lung rdf:type obo:MA_0000415 ; # This is a mouse lung sift:part-of :group1-cage1-1 . # part of :group1-cage1-1
:group1-cage1-1-lung-hyperplasia rdf:type obo:MPATH_134 ; # This is a mouse hyperplasia obo:BFO_0000052 :group1-cage1-1-lung ; # in :group1-cage1-lung sift:severity sift:mild . # has severity: mild
Create CEBS Application Ontology, Rules to capture SIFT relationshipsand tools to convert SIFT to ttl …..James A Overton
Start with SIFT Tabular Data (implicit relationships)
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Final aims
• RDF triple store
• This is Linked Data*, structured and computer-readable
*Tim Berners-Lee (2006-07-27). "Linked Data—Design Issues". W3C. Retrieved 2010-12-18 at http://en.wikipedia.org/wiki/Linked_data
• Over which we can write SPARQL and other computational queries to produce summary reports
• Which will be available for use on the Semantic Web
• Which will be available for download
• Which users can query in new user interface
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Recapping
• Examples of use
– Data for an individual study
– Cross-study query
– Cross-domain review of results
• CEBS practices
– Capture of meta data and data
– CEBS data dictionary
– SIFT files
• CEBS project towards Linked Data
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Thanks• Laura Hall (POB)
• Vistronix team – Asif Rashid– Julie Berke-Law, Phyllis Brown, Kevin Church, James Faison, Cari
Favaro, Hui Gong, Mary Hicks, Isabel Lee, Justin Johnson, Jeremy McNabb, Robert Mullen, Anand Paleja, Veronica Pham, Mike Shaw
– James A Overton (CEBS Application Ontology)