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Data Integration vs Transparency: Tackling the tension
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Transcript of Data Integration vs Transparency: Tackling the tension
Paul Groth Elsevier Labs@pgroth | pgroth.com
Data Integration & TransparencyTackling the tension
University of Fribourg Informatics Colloquium June 15, 2015
Outline
• Data integration for analysis– i.e. remixing data
• The need for transparency• Provenance as a solution• The downloads folder problem
60 % of time is spent on data preparation
http://[email protected]
@Open_PHACTS
Why?
Public Domain Drug Discovery Data:Pharma are accessing, processing, storing & re-processing
LiteraturePubChem
GenbankPatents
DatabasesDownloads
Data Integration Data AnalysisFirewalled Databases
Repeat @ each
companyx
Prioritised Research QuestionsNumber sum Nr of 1 Question
15 12 9 All oxido,reductase inhibitors active <100nM in both human and mouse
18 14 8Given compound X, what is its predicted secondary pharmacology? What are the on and off,target safety concerns for a compound? What is the evidence and how reliable is that evidence (journal impact factor, KOL) for findings associated with a compound?
24 13 8 Given a target find me all actives against that target. Find/predict polypharmacology of actives. Determine ADMET profile of actives.
32 13 8 For a given interaction profile, give me compounds similar to it.
37 13 8 The current Factor Xa lead series is characterised by substructure X. Retrieve all bioactivity data in serine protease assays for molecules that contain substructure X.
38 13 8 Retrieve all experimental and clinical data for a given list of compounds defined by their chemical structure (with options to match stereochemistry or not).
41 13 8
A project is considering Protein Kinase C Alpha (PRKCA) as a target. What are all the compounds known to modulate the target directly? What are the compounds that may modulate the target directly? i.e. return all cmpds active in assays where the resolution is at least at the level of the target family (i.e. PKC) both from structured assay databases and the literature.
44 13 8 Give me all active compounds on a given target with the relevant assay data46 13 8 Give me the compound(s) which hit most specifically the multiple targets in a given pathway (disease)59 14 8 Identify all known protein-protein interaction inhibitors
www.openphacts.org
Research question 15: All oxido reductase inhibitors active < 100nM in both human and mouse
From Mabel Loza - USC team
From Mabel Loza - USC team
From Mabel Loza - USC team
From Mabel Loza - USC team
Research question 15: All oxido reductase inhibitors active < 100nM in both human and mouse
ChEMBL:
Search target Oxidoreductase: 481 targets from different species
Selection of all the oxidoreductases and filtering bioactivities with the criteria IC50 < 100 (no units could be selected): 11497 data obtained
Table exported to a excel spreadsheet and manually filtered
From Mabel Loza - USC team
5 people
Working 6 hours
Problem: Data Integration
DataSource
DataSource
Data Warehouse
Queries
ExtractTransformLoad
DataSource
DataSource
Mediator
Queries
QueryReformulation
Using the Power of Open PHACTS, London, 22-23 April 2013
RDFNanopub
Db
VoID
Data Cache (Virtuoso Triple Store)
Semantic Workflow Engine
Linked Data API (RDF/XML, TTL, JSON)DomainSpecificServices
Identity Resolution
Service
Chemistry RegistrationNormalisation & Q/C
IdentifierManagement
Service
index
Co
re P
latf
orm
P12374EC2.43.4
CS4532
“Adenosine receptor 2a”
RDF
VoID
Db
RDFNanopub
Db
VoID
RDF
Db
VoID
RDFNanopub
VoID
Public Content Commercial
Public Ontologies
User Annotations
Applications
16
Open PHACTS Explorer
17
Open PHACTS Explorer
?
Credits: Curt Tilmes, Peter Fox
Tilmes, C.; Fox, P.; Ma, X.; McGuinness, D.L.; Privette, A.P.; Smith, A.; Waple, A.; Zednik, S.; Zheng, J.G., "Provenance Representation for the National Climate Assessment in the Global Change Information System," Geoscience and Remote Sensing, IEEE Transactions on , vol.51, no.11, pp.5160,5168, Nov. 2013
Problem: I don’t trust your assessment what is it based on?
Tension:
Integrated & SummarizedData
Transparency& Trust
Solution
Integrating and exposing provenance provided by multiple sources
provbook.org
National Climate Change Assessment Provenance
Tooling
http://asdf.readthedocs.org/en/latest/provenance.html
http://www.slideshare.net/soilandreyes/20130529-taverna-provenance
Towards Workflow Ecosystems Through Semantic and Standard Representations Garijo, D.; Gil, Y.; and Corcho, O. In Proceedings of the Ninth Workshop on Workflows in Support of Large-Scale Science (WORKS), held in conjunction with the IEEE ACM International Conference on High-Performance Computing (SC), New Orleans, LA, 2014.
https://github.com/pgroth/PROVTutorial
Great…..
but
Data integration is manual
Look to OS techniques
1. Taint Tracking2. Record and Replay
Work with Manolis Stamatogiannakis & Herbert Bos VU University Amsterdam – Security Group
https://www.youtube.com/watch?v=BD0h6M5mVoo
http://www.androidreran.com
Use R&R for provenance
1. Execution Capture2. Application of instrumentation3. Provenance analysis4. Selection and iteration
Implemented using plugins for Platform for Architecture-Neutral Dynamic Analysis (PANDA)
An Example (1)
<exe://pam-foreground-~3451> prov:endedAtTime 199090196 .<exe://getent~3451> a prov:Activity . <exe://getent~3451> rdf:type dt:getent .<exe://cut~3452> a prov:Activity . <exe://cut~3452> rdf:type dt:cut .<file:/etc/nsswitch.conf> a prov:Entity .<file:/etc/nsswitch.conf> rdfs:label "/etc/nsswitch.conf" .<file:/etc/nsswitch.conf> rdf:type dt:Unknown .<exe://getent~3451> prov:used <file:/etc/nsswitch.conf> .# unused file:3477815296:getent~3451:/etc/passwd:r0:w0:f524288<exe://getent~3451> prov:startedAtTime 199090196 .<exe://getent~3451> prov:endedAtTime 200392668 .<file:FD0_3452> a prov:Entity .<file:FD0_3452> rdfs:label "FD0_3452"
An Example (2
Example (3)
Example (4)
Conclusion
• Tension between: – putting stuff together; and– documenting what’s been done
• Provenance helps• Issues in collection • Standards + Stealth1
1 hat tip Carole Goble
Questions?
• More info:– openphacts.org– data2semantics.org– provbook.org– https://github.com/m000/dtracker– Manolis Stamatogiannakis, Paul Groth and Herbert Bos. Decoupling
Provenance Capture and Analysis from Execution. Theory and Practice of Provenance 2015
– Luc Moreau, Paul Groth, James Cheney, Timothy Lebo, Simon Miles, The rationale of PROV, Web Semantics: Science, Services and Agents on the World Wide Web, Available online 20 April 2015 http://dx.doi.org/10.1016/j.websem.2015.04.001.
– Paul Groth, "Transparency and Reliability in the Data Supply Chain," IEEE Internet Computing, vol. 17, no. 2, pp. 69-71, March-April, 2013
– Paul Groth, "The Knowledge-Remixing Bottleneck," Intelligent Systems, IEEE , vol.28, no.5, pp.44,48, Sept.-Oct. 2013