Transcriptomics

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Transcriptomics

• Patrick Kemmeren
• European Bioinformatics Institute
• Genomics Lab, UMC Utrecht

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What are microarrays ?
Transcriptomics?
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Experiment
genes
Sample
Sample
Sample
Sample
Sample
Array design
RNA extract
RNA extract
RNA extract
RNA extract
RNA extract
hybridisation
hybridisation
labelled nucleic acid
array
hybridisation
hybridisation
hybridisation
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Microarray data and annotation
Samples
Gene expression matrix
Genes
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Traditions of data sharing in Life Sciences

• Data used in publications should be made
  available so that
• the experiments can be reproduced and the
  conclusions can be verified
• the others can build on others results
• In genome sequencing this has evolved into
  submissions to public sequence databases
  DDBJ/EMBL/Genbank most journals require such
  submissions

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Sharing microarray data which data?
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MGED standards - MIAME
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MGED MIAME
MIAME 6 parts of a microarray experiment
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Microarray experiment
Labelled Extracts Colours related to labels
Hybridizations Shapes related to array designs
Samples
Extracts
Experiment name
Rustici et al., S. pombe cell-cycle mutant data
(2004)
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ExternalApplication
MAGE-ML
Submission support
Curation
Database Architecture
XML
MAGE-ML
Visualisation
Data download
Data upload
User Functionality
Retrieval of raw processed data for analysis
Submissions Database
Gene, sample, and experiment centric queries,
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MIAMExpress

• Submission and annotation tool
• Potential local data annotation tool
• Based on MIAME concepts
• Accepts protocol, array and experiment
  submissions
• User accounts allow re-use of protocols and
  arrays
• Works with your own or commercial arrays

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MIAMExpress schema
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ExternalApplication
MAGE-ML
Submission support
Curation
Database Architecture
XML
MAGE-ML
Visualisation
Data download
Data upload
User Functionality
Retrieval of raw processed data for analysis
Submissions Database
Gene, sample, and experiment centric queries,
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ArrayExpress

• http//www.ebi.ac.uk/arrayexpress
• A public repository for microarray data at the EBI

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Online (MIAMExpress)Submissions
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ArrayExpress data - by organism
Total 7000 hybridisations
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ExternalApplication
MAGE-ML
Submission support
Curation
Database Architecture
XML
MAGE-ML
Visualisation
Data download
Data upload
User Functionality
Retrieval of raw processed data for analysis
Submissions Database
Gene, sample, and experiment centric queries,
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Gene-centric Query Prototype
http//www.ebi.ac.uk/aedw/ArrayExpress_main.html
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Gene-centric Query Prototype
- Driven by a BioMart backend
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Gene-centric Query Prototype
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ExternalApplication
MAGE-ML
Submission support
Curation
Database Architecture
XML
MAGE-ML
Visualisation
Data download
Data upload
User Functionality
Retrieval of raw processed data for analysis
Submissions Database
Gene, sample, and experiment centric queries,
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Expression Profiler

• http//www.ebi.ac.uk/expressionprofiler
• An online microarray data analysis platform

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What can you do with the data?
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What can you do with the data?
Expression ProfilerData Viewer Component
...view as a heatmap...
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What can you do with the data?
Expression ProfilerHierarchical Clustering
Component
...cluster the data...
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What can you do with the data?
...look at GeneOntology enrichment of a selected
cluster ...
Expression ProfilerGO Annotation Component
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What can you do with the data?
... check out how clusterings compare ...
Expression ProfilerClustering Comparison
Component
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What can you do with the data?
... integrate several data types together ...
Expression ProfilerThreeway Similarity Analysis
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Available Components

• Data Selection
• Data Transformation
• Missing Value Imputation
• Hierarchical Clustering K-groups Clustering
• Clustering Comparison
• Signature Algorithm

• Sequence Homology
• SPEXS Promoter Discovery
• Visual Pattern Matching
• Ordination (COA, PCA)
• Between Group Analysis
• Three-way Similarity Analysis
• GO Annotation

• Uses
• ArrayExpress suite of tools
• Standalone tool
• Locally installed (UJI, UMC Utrecht)
• Teaching tool
• Pipelines, workflows, high-throughput analysis

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• Original EP Development
• Jaak Vilo (Tartu)
• Patrick Kemmeren (Utrecht)
• Misha Kapushesky
• EPNG Framework Development
• Patrick Kemmeren (Utrecht)
• Misha Kapushesky
• Caroline Johnston (UCL)
• Visualization Components
• Misha Kapushesky
• Steffen Durinck (Leuven)
• Phil Hyoun Lee

Acknowledgements
EBI Microarray Informatics TeamAlvis Brazma,
Head of Microarray Informatics Group Ahmet
Oezcimen, Scientist (Oracle DBA) Anastasia
Samsonova, PhD student Anjan Sharma, Scientist
(Software Developer) Anna Farne, Scientist
(Curation) Aurora Torrente, PhD Student Bhuwan
Tiwari, Trainee Catherine Leroy, Summer
Student Ele Holloway, Scientist
(Curation) Gabriella Rustici, Scientist
(Postdoc) Gaurab Mukherjee, Scientist
(Curation) Gonzalo Garcia Lara, Scientist (Web
Designer/Programmer) Helen Parkinson, Scientist
(Curation Coordinator) Jaak Vilo, Consultant Lev
Soinov, Scientist (Postdoc Wellcome Trust) Misha
Kapushesky, Scientist (Scientific Application
Programmer) Mohammadreza Shojatalab, Scientist
(Database Programmer) Niran Abeygunawardena,
Scientist (Web Designer/Programmer)Patrick
Kemmeren, Consultant Per Lilja, Scientist
(Database Programmer) Philippe Rocca-Serra,
Scientist (Nutrigenomics Proj. Coordinator) Pierre
Marguerite, Summer Student Richard Coulson,
Scientist (Biosapiens Project) Sergio Contrino,
Scientist (Database Programmer) Steffen Durinck,
Student Susanna-Assunta Sansone, Scientist
(Toxicogenomics Proj. Coordinator)Tim
Rayner, Scientist (Curation) Ugis Sarkans,
Scientist (Database Development Coordinator)

• Clustering Comparison
• Aurora Torrente
• Christine Körner (Leipzig)
• PCA/COA/BGA
• Aedín Culhane (Cork)
• Signature Algorithm
• Jan Ihmels (Tel-Aviv)
• Gene Ordering
• Karlis Freivalds (Riga)
• Normalisation
• Caroline Johnston (UCL)
• Web Services
• Antonio Estruch (UJI)