Bioinformatics and Toxicology

Philipp Antczak

What is Bioinformatics?

• It is the application of statistics and computer science to the field of molecular biology and medicine.

– Analysis of Cancer mutations

– Analysis of Gene Expression

– DNA Sequence Analysis

– Simulations and Modelling

– etc

Tools

• Sequence Analysis Tools – DNA sequence analysis

• Image Processing – Microarray image analysis

• Exploratory Algorithms – Principle Component Analysis (PCA) – Hierarchical clustering

• Statistical Tests – Identify differentially expressed features – Classification algorithms – Modelling

• Networks – Building large networks based on high density data – Identifying sub-networks which may be indicative of

Case Study – Applying Bioinformatics to a problem in Toxicology

Daphnia Magna

• Wide Geographic Distribution

• Central role in freshwater food webs

• Ability to adapt to a range of habitats

• Highly sensitive to anthropogenic chemicals

• Analysed their gene expression using microarrays

The aims of this project

• Identify whether similar chemicals (such as metals or a specific subgroup) act similarly on an organism

• Is it possible to apply methodologies developed in biomedical research to toxicology?

• Identify whether Daphnia magna can be used to sense specific chemicals in a sample

The Dataset

• Dataset was provided by Chris Vulpe laboratory at the University of California, Berkley

• 14 day adult D. magna

– Exposed these to the 36 chemicals at 1/10 of measured LD50

Data

Can we predict chemical class from gene expression

profiles?

Can we predict measured Toxicity (LD50)?

Exploratory Analysis

PCA of Dataset

Benzene Endocrine Herbicide Industrial Metals Organophosphates Pyrethroids

Hierarchical Clustering of Differentially Expressed Genes

Classification

How well can I predict a chemical group?

Regression Modelling

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Can we predict Toxicity?

Other Applications

• Water quality assessment – Predicting what is in the water we drink using for

example Daphnia Magna

• Drug Development – Will a new drug be effective?

• Biomedical research – Develop drugs specific for human diseases

– Provide the population with better foods, i.e. less pesticides or other toxins

Acknowledgments

University of Birmingham Dr. Francesco Falciani – Systems Biology Nil Turan Kim Clarke Wazeer Varsally Rita Gupta Jaanika Kronberg Helani Munasinghe Prof. Mark Viant– local Daphnia Experts Thomas White

University of California, Berkeley Prof. Chris Vulpe – U.S. Partners, data acquisition Leona Scandlan