BCU 2013

The Inves)ga)on/Study/Assay (ISA) metadata framework for reproducible and reusable bioscience research

Alejandra González-‐Beltrán, PhD on behalf of the ISATeam

Oxford e-‐Research Centre, University of Oxford

Faculty of Technology, Environment and Engineering Birmingham City University

12th March 2013

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

h[p://www.nature.com/news/2011/110111/full/469139a.html


h[p://www.economist.com/node/21528593


h[p://www.economist.com/node/21528593 h[p://www.ny)mes.com/2011/07/08/health/research/08genes.html

Contextual informa)on (metadata): •  Sample characteris)cs •  Technology and measurement types •  Instrument parameters •  …

Need for a generic representa)on, applied to: •microarray based experiments (MAGE) •sequencing based experiments (SRA) •flow cytometry based experiments (FuGE-‐Flow Cyt) •mass spectrometry and NMR spectroscopy

experiments (Metabolights and PRIDE)

Roadmap

Reproducible & Reusable Bioscience Research

Roadmap


Well-‐annotated & Structured Data

reasoning

analysis

exchange

integra)on

visualiza)on

browsing retrieval

Roadmap



reasoning

analysis

exchange

integra)on

visualiza)on

browsing retrieval

User community

Roadmap



reasoning

analysis

exchange

integra)on

visualiza)on

browsing retrieval

Community Standards Sodware Tools

User community

Roadmap


reasoning

analysis

exchange

integra)on

visualiza)on

browsing retrieval

Source of the figure: EBI website

§  Interdisciplinary and integra:ve in character •  need to deal with new and exis:ng datasets

•  deal with a variety of data types

Bioscience is mul)-‐domain…

tox/pharma

env

health

agro

Mul)ple communi)es, mul)ple norms and standards, e.g.:

report the same core, essen)al informa)on

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

130 +

Es:mated

150 +

Source: MIBBI, EQ

UATO

R

303 +

Source: BioPortal Databases, annota)on, cura)on 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 repor)ng 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 standards just

for biomedical applica)ons?

What are the criteria to evaluate their status and

value?

How can I get involved to propose

extensions or modifica)ons?

Which tools and databases

implement which standards?

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

me?

Which formats support specific

minimum informa)on 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, publica:ons, tools and databases

•  Assessment criteria for usability and popularity of standards

•  Rela:onships among standards

•  Encouragement for communica:on & interac:on among groups

•  Promo)ng interoperability & informed decisions about standards

infrastructure

•  Assist in the annota)on and management of experimental metadata at source, suppor)ng data provenance tracking

•  Deal with high-‐throughput studies using one or a combina)on of omics and other technologies

•  Empower users to uptake community-‐defined checklists and ontologies

•  Facilitate data sharing, re-‐use, comparison and reproducibility of experiments, submission to interna)onal public repositories

infrastructure ISA sodware suite: suppor)ng standards-‐compliant experimental annota)on and enabling cura)on at the community level Rocca-‐Serra et al, 2010 Bioinforma)cs

faahKO dataset •  Available in Bioconductor •  Subset of the original data on global metabolite profiling

•  LC/MS peaks from the spinal cords of 6 wild-‐type and 6 FAAH (fa[y acid amyde hydrolase) knockout mice

Saghatlian et al. Biochemistry. 2004

faahKO inves)ga)on -‐ Define key en))es (e.g. factors, protocols, parameters) -‐ Grouping of studies -‐ Relate studies and assays

faahKO study

NEWT UniProt Taxonomy Database Mouse Genome Informa)cs

-‐  Subjects studied: source(s), sampling methodology, characteris)cs -‐  treatments/manipula)ons performed to prepare the specimens

faahKO study

Mouse Adult Gross Anatomy

-‐  Subjects studied: source(s), sampling methodology, characteris)cs -‐  treatments/manipula)ons performed to prepare the specimens

faahKO assay -‐  measurement type, e.g. metabolite profiling -‐  technology, e.g. mass spectrometry

Create template(s) to fit the type of experiments to be described

Create templates detailing the steps to be reported for different inves)ga)ons, complying to community standards, e.g. configuring the value(s) allowed for each field to be •  text (with/without regular expression tes)ng), •  ontology terms, •  numbers etc.

Describe, curate your experiment using a desktop-based tool

Report and edit the description using this tool, (also customized using the templates) with a spreadsheet like look and feel, packed with functionalities such as •  ontology search (access via ) •  term-tagging features •  import from spreadsheets etc…

•  Ontology search and automated tagging (relying on NCBO Bioportal services) on Google Spreadsheets •  Collabora)ve annota)on; support for distributed users •  Version control & history

OntoMaton: a Bioportal powered Ontology widget for Google Spreadsheets Maguire et al, 2013 Bioinforma)cs

•  R package available in BioConductor 2.11 h[p://bioconductor.org/packages/release/bioc/html/Risa.html

•  ISAtab class •  Read ISAtab files into ISAtab objects and write ISAtab files back to disk

•  Increment metadata with defini)on factors/treatments/groups

•  Build xcmsSet (xcms package) objects from mass spectrometry assays

•  Augment the ISAtab dataset ader analysis •  source & issues tracking

h[ps://github.com/ISA-‐tools/Risa

•  faahKO package v. 2.12 contains ISAtab files describing the experiment faahkoISA = readISAta(find.package("faahKO")) assay.filename <-‐ faahkoISA["assay.filenames"][[1]] xset = processAssayXcmsSet(faahkoISA, assay.filename) … updateAssayMetadata(faahkoISA, assay.filename,"Derived Spectral Data File","faahkoDSDF.txt" )

•  MTBLS2 processing and analysis using Risa, xcms and CAMERA BioConductor packages

Metabolights – an open access general-purpose repository for metabolomics studies and associated meta-data Haug et al, 2012 Nucleic Acids Research

The implicit seman)cs of the syntax

Protocol Process

Characteristics[…] Factor Value[…] (independent variables) Material Type Comment[…]

Date (day effect)

Performer (operator effect)

Parameter Value […]

Derived Data File

Raw Data File

Data File Node

" DATA!

" Material!

Material Node

Sample Name Material Type

Hybridiza)on Assay Name Assay Design REF Array Data File Protocol REF Derived Array Data File

sample1 genomic DNA assay1 A-AFFY-107" assay1.cel data normaliza)on assay1.txt



Material transforma)ons...

" Material!

" DATA!

Tagging: from free text to ontology-‐based • single interven)on representa)on, free text annota)on

• single interven)on, ontology-‐based annota)on

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Source Name Characteris)cs[organism]

Factor Value[perturba)on agent]

Factor Value[dose]

Factor Value[dura)on]

individual1 human aspirin high dose 12 weeks

Source Name Characteris)cs[organismobi:0100026)])

Term Source REF

Term Accession Number

Factor Value[chemical compound CHEBI_37577)]

Term Source REF


individual1 Homo sapiens NCBITax 9606 aspirin CHEBI 1231354

Factor Value[dose(OBI_0000984)

Term Source REF


Factor Value[)me (PATO_0000165)] Unit Term Source

REF Term Accession Number

low dose LNC LP30872-‐3 12 week UO “0000034”

Kohonen et al. The ToxBank Data Warehouse: a research cluster of 7 EU FP7 Health systems toxicology and toxicogenomics projects.

Health Care & Life Sciences Interest Group

ToxBank effort developed by Nina Jeliazkova

•  Make the seman)cs of ISAtab explicit, including materials & data en))es & processes & their rela)onships

•  Provide incen)ves for provision of ontology-‐based annota)ons in ISA-‐TAB datasets; exploit those annota)ons

•  Augment ISA syntax with new elements (e.g. groups), facilita)ng the understanding & querying of experimental design

•  Facilitate data integra)on & knowledge discovery/reasoning

architecture

ISA-‐TAB parser isa2owl mapping

parser graph analysis

Configura)on file

Implementa)on: -‐  java-‐based -‐  Using owlapi

Expe

rimen

tal

domain

Biomolecular domain

Chemical domain

Informa)on domain

vocabularies


Term Source REF



Term Source REF




Term Source REF



Term Source REF



OBI

GO ChEBI IAO

Open Biological and Biomedical Ontologies (OBO) Foundry BFO

ISA-‐OBI mapping

ISA-‐SIO mapping

Data subset: LC/MS peaks from the spinal cords of 6 wild-‐type and 6 FAAH (fa[y acid amyde hydrolase) knockout mice

faahKO dataset Available in Bioconductor (with ISA-‐TAB metadata) Global metabolite profiling

•  support different conversion modes (different levels of granularity)

•  querying for ISA-‐TAB datasets, across mul)ple experiment types

•  reasoning exploi)ng ontology annota)ons –  seman)c valida)on of ISA-‐TAB datasets

•  augmented annota)on over na)ve ISA syntax –  iden)fica)on gaps in ontological representa)ons –  feedback of findings to community ontologies

Increasing level of structure for experimental metadata

Notes in Lab books

Spreadsheets & Tables (ISAtab metadata)

Facts as RDF statements

A growing ecosystem of over 30 public and internal resources using the ISA metadata tracking framework to facilitate standards-‐compliant collec)on, cura)on, management and reuse of inves)ga)ons in an increasingly diverse set of life science domains.

Towards interoperable bioscience data Sansone et al, 2012 Nature Gene)cs

Implementa)on at Harvard

ISA

h[p://discovery.hsci.harvard.edu/

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Implementa)on at the European Bioinforma)cs Ins)tute

h[p://www.ebi.ac.uk/m

etabolights


reasoning

analysis

exchange

integra)on

visualiza)on

browsing retrieval

@isatools @biosharing isa-‐tools.org

isacommons.org biosharing.org

BCU 2013

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