Tutorial 1: Pathway Creation CSIRO Tutorial Series: Pathway and Network Analysis

CSIRO NUTRITION & FOOD

Martina Summer-Kutmon, PhD | Department of Bioinformatics, Maastricht University, The Netherlands 24 November 2015

Who am I?

Martina Summer-Kutmon Postdoctoral researcher • Department of Bioinformatics at Maastricht University in the

Netherlands (Chris Evelo’s group)

Research focus: • Application of network-based approaches in biomedical research

(pathways & networks) • Processes involved in the development of chronic diseases in

obese subjects • Architect of WikiPathways and developer of pathway and network

analysis tools and methods

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Tutorial series

• Tutorial 1: Pathway creation • 24 November 2015, 2-4 PM

• Tutorial 2: Pathway analysis • 1 December 2015 , 2-4 PM

• Tutorial 3: Network analysis • 8 December 2015 , 2-4 PM

• Material (presentations and hands-on instructions) will be available on the website

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Why Pathways and Networks?

Data analysis

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Quantitative measurements

Isolated data points

Slide adapted from Thomas Kelder

Data analysis

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Comparative statistics

Isolated lists

Clustering

Isolated groups

Gene sets

Functional groups

Slide adapted from Thomas Kelder

Data analysis

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Functional organisation

Pathways

Slide adapted from Thomas Kelder

Data analysis

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Important

link!

Systems organisation

Networks

Slide adapted from Thomas Kelder

Pathway creation

Tutorial series

• Definition on Wikipedia: • “ A biological pathway is a series of interactions among molecules in a cell

that leads to a certain product or a change in a cell.

• Types of pathways: • Metabolic pathways

• Gene regulation pathways

• Signal transduction pathways

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http://www.genome.gov/multimedia/illustrations/Biological_Pathways.pdf

Metabolic pathways

• “... series of chemical reactions occurring within a cell that are catalysed by enzymes.”

• Example: glycolysis

http://wikipathways.org/index.php/Pathway:WP534

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Metabolic pathways

http://en.wikipedia.org/wiki/Metabolic_pathway

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Gene regulation pathways

• Pathways that regulate the level of gene expression

• Often sub-pathways in larger pathways

• Linked to gene-regulatory networks

http://en.wikipedia.org/wiki/Gene_regulatory_network

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Signal transduction pathways

https://en.wikipedia.org/wiki/Signal_transduction

Extracellular signal

• activates receptor

• triggers response

• Response can be

change in metabolism, gene expression, cell shape, cell death, ...

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Pathway resources

• Pathguide.org http://www.pathguide.org/ • More than 100 pathway related resources

• Pathway diagrams and annotated pathway models

• Commonly used pathway databases are: • Reactome

• WikiPathways

• KEGG

• PANTHER

• BioCyc

• ...

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Pathway resources

• BUT ... a lot of information is still missing

2. Knowledge carefully hidden in:

1. Exact protein function not known

Only ~50% of the known human genes are present in

pathways

Unstructured literature Researchers’ minds

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WikiPathways

www.wikipathways.org

A Wikipedia for pathways:

• Everybody can contribute and share pathways

• Everybody can edit and curate pathways

• Everybody can use the pathway collection

• Not just diagrams but fully annotated models

• Changes can be reverted easily

• New findings can be added immediately

• Interactive pathway viewer

• Offline editor and analysis tool PathVisio

• Collaboration with other pathway databases (e.g. Reactome)

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PathVisio

Pathway editor, analysis and visualization toolbox

www.pathvisio.org

• Tutorial 1: • drawing and editing of pathways

• Tutorial 2: • analysis and visualization of data

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Not just an image!

Relations, Annotations

Literature references

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Pathway models

Hands on session

• Creating an example pathway • Drawing + annotating

• Transport of vitamin B12

• Based on figure in publication

• What will you learn today? 1. Drawing a pathway in PathVisio

2. Annotation of elements in the pathway – why and how?

3. Adding publication references

4. Submission and upload to WikiPathways

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Hands on

Nielsen et al (2012) Vitamin B12 transport from food to the body’s cells - a sophisticated, multistep pathway Pubmed: 22547309

Turn a static image into a WikiPathways pathway so it can

be used in pathway analysis

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Questions

CSIRO NUTRITION & FOOD

Email: martina.kutmon@maastrichtuniversity.nl

Information and material: http://projects.bigcat.unimaas.nl/adelaide-tutorials-2015/

Let’s get started.