Drug Discovery- ELRIG -2012

Alejandra González-‐Beltrán, PhD

Senior Software Engineer, ISATeam University of Oxford e-‐Research Centre, Oxford, UK

Drug Discovery 2012, Manchester, UK, September 6-‐7

Community-‐standards for reproducible and reusable research -‐

fundamentals and challenges

Ioannidis et al., Repeatability of published microarray gene expression analyses. Nature Gene*cs 41(2), 149-‐55 (2009) doi:10.1038/ng.295

Ioannidis et al., Repeatability of published microarray gene expression analyses. Nature Gene*cs 41(2), 149-‐55 (2009) doi:10.1038/ng.295

Roadmap

Reproducible & Reusable Bioscience Research

Principles & Challenges

Roadmap


Well-‐annotated & Structured Data

reasoning

analysis

exchange

integraYon

visualizaYon

browsing retrieval


Roadmap



reasoning

analysis

exchange

integraYon

visualizaYon

browsing retrieval


Community Standards So[ware Tools

Source of the figure: EBI website

§  Interdisciplinary and integra9ve in character •  need to deal with new and exis9ng datasets

•  deal with a variety of data types

Bioscience is mulY-‐domain…

tox/pharma

env

health

agro

The International Conference on Systems Biology (ICSB), 22-28 August, 2008 Susanna-Assunta Sansone www.ebi.ac.uk/net-project

From reusable data to reproducible research

To make the datasets comprehensible and interoperable, underpinning future

invesYgaYons, we need common ways to report and share the experimental details

and the associated results

Consistent reporYng will have a posiYve and long-‐lasYng impact on the value of

collec9ve scien9fic outputs.

Community Standards

Different communiYes, different norms and standards, e.g.:

report the same core, essenYal informaYon

use the same term to refer to the same ‘thing’ allow data to flow from

one system to another

Different communiYes, different norms and standards, e.g.:

report the same core, essenYal informaYon

use the same term to refer to the same ‘thing’ allow data to flow from

one system to another

Challenges: lack of interaction and coordination, duplication of effort, fragmentation and uneven coverage…hinders interoperability

GIATE Guidelines for InformaYon About Therapy Experiments

Clinical Model

Animal Model

Cellular Model

Molecular Model

TherapeuYc InvesYgaYon

Molecular Model

Cellular Model

Animal Model

Clinical Model

Generic Model

VO!

miame!MIAPA!

MIRIAM!MIQAS!MIX!

MIGEN!

CIMR!MIAPE!

MIASE!

MIQE!

MISFISHIE….!

REMARK!

CONSORT!

MAGE-Tab!GCDML!

SRAxml!SOFT! FASTA!

DICOM!

MzML!SBRML!

SEDML…!

GELML!

ISA-Tab!

CML!

MITAB!

AAO!CHEBI!

OBI!

PATO! ENVO!MOD!

BTO!IDO…!

TEDDY!

PRO!XAO!

DO

Growing number of bioscience reporYng standards

GIATE!

130 +

Es9mated

150 +

Source: MIBBI, EQ

UATO

R

303 +

Source: BioPortal Databases, annotaYon, curaYon tools

miame!MIAPA!

MIRIAM!MIQAS!MIX!

MIGEN!

CIMR!MIAPE!

MIASE!

MIQE!

MISFISHIE….!

REMARK!

CONSORT!

MAGE-Tab!GCDML!

SRAxml!SOFT! FASTA!

DICOM!

MzML!SBRML!

SEDML…!

GELML!

ISA-Tab!

CML!

MITAB!

AAO!CHEBI!

OBI!

PATO! ENVO!MOD!

BTO!IDO…!

TEDDY!

PRO!XAO!

DO

VO!GIATE!

Growing number of bioscience reporYng standards

But… what do we know about them and how they are related

miame!MIAPA!

MIRIAM!MIQAS!MIX!

MIGEN!

CIMR!MIAPE!

MIASE!

MIQE!

MISFISHIE….!

REMARK!

CONSORT!

MAGE-Tab!GCDML!

SRAxml!SOFT! FASTA!

DICOM!

MzML!SBRML!

SEDML…!

GELML!

ISA-Tab!

CML!

MITAB!

AAO!CHEBI!

OBI!

PATO! ENVO!MOD!

BTO!IDO…!

TEDDY!

PRO!XAO!

DO

VO!GIATE!

Which ones are mature enough for

me to use or recommend?

I work on plants, are these just for biomedical applicaYons?

What are the criteria to evaluate their status and

value?

How can I get involved to propose

extensions or modificaYons?

Which tools and databases

implement which standards?

I use high throughput sequencing technologies, which ones are relevant to

me?

Which formats support specific

minimum informaYon guidelines?

But… what do we know about them and how they are related

A coherent, curated and searchable catalogue of data sharing resources

•  Bioscience standards and

associated data-‐sharing policies, publica9ons, tools and databases

•  Assessment criteria for usability and popularity of standards

•  Rela9onships among standards

•  Encouragement for communica9on & interac9on among groups

•  PromoYng interoperability & informed decisions about standards


Standards compliance is challenging…

Is it possible to achieve a common, structured representaYon

of diverse bioscience experiments that:

•  transcends individual bioscience domains, but also

•  follows the appropriate community norms and standards?

§  Capture all salient features of the experimental workflow

§  Make annotaYon explicit and discoverable

§  Structure the descripYons for consistency, tracking §  independent variables §  dependent variables and using §  resolvable idenYfiers and

cross-‐references

Structured descripYon of datasets

§  We must strike a balance between sufficiency and pracYcability: •  depth and breadth of

informaYon •  burden to produce and

maintain the informaYon

Not too much, not too lille, just ‘right’

MAGE-Tab Pride-xml

SRA-xml SOFT

Metadata tracking framework, designed to support the use of several standards c h e c k l i s t s , t e r m i n o l o g i e s a n d conversions to (a growing number of) other metadata formats , used by public repositories, e.g.


user community

ISA soQware suite: supporYng standards-‐compliant experimental annotaYon and enabling curaYon at the community level (Rocca-‐Serra et al, 2010)


23

empowering researchers to use standards

Ontology Search and Tagging in Google Spreadsheets

Ontology Search and Tagging in Google Spreadsheets

ISA infrastructure & linked data

•  Work in progress to convert to RDF/OWL to connect to the growing Linked Data universe RDF = Resource DescripYon Framework, OWL = Web Ontology Language

•  CollaboraYons with Toxbank & W3C HCLSIG

<subject, predicate, object> <lipoprotein> <parYcipates_in> <inflammatory response> <PRO:212342352> <BFO_0000056> <GO:0006954>

Increasing levels of structure…

Notes in Lab Books(information for humans)

Spreadsheets and Tables( the compromise)

Facts as RDF statements(information for machines)

A growing ecosystem of over 30 public and internal resources using the ISA metadata tracking framework to facilitate standards-‐compliant collec9on, cura9on, management and reuse of invesYgaYons in an increasingly diverse set of life science domains, including:

•  environmental health •  environmental genomics •  metabolomics •  metagenomics •  nanotechnology •  proteomics,

We aim to achieve a common representaYon of experimental content that transcends

individual bioscience domains

Sansone et al., Towards interoperable bioscience data. Nature Genetics 44, 121-126 (2012) doi:10.1038/ng.1054

•  stem cell discovery •  system biology •  transcriptomics •  toxicogenomics •  also by communiYes working to build a

library of cellular signatures

Nanotechnology InformaYcs Working

Group

Some of the internal projects: Some of the public groups/resources:

4

Stem Cell Commons

Stem Cell Commons

A growing ecosystem of over 30 public and internal resources using the ISA metadata tracking framework to facilitate standards-‐compliant collec9on, cura9on, management and reuse of invesYgaYons in an increasingly diverse set of life science domains, including:

•  environmental health •  environmental genomics •  metabolomics •  metagenomics •  nanotechnology •  proteomics,

•  stem cell discovery •  system biology •  transcriptomics •  toxicogenomics •  also by communiYes working to build a

library of cellular signatures

Implementation at Harvard

ISA

hlp://discovery.hsci.harvard.edu/

31

Implementation at the EBI

hlp://www.ebi.ac.uk/metabolights

lack of coordinaYon,

fragmentaYon and uneven coverage

Standards-‐compliant data sharing is demanding and Yme-‐consuming

GIATE Guidelines

Terminologies

Formats



reasoning

analysis

exchange

integraYon

visualizaYon

browsing retrieval

Community Standards So[ware Tools

@isatools @biosharing Isa-‐tools.org isacommons.org biosharing.org

Business

Drug Discovery- ELRIG -2012