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Meet Me Halfway: When Genomics Meets Structural Bioinformatics

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Abstract

The DNA sequencing technology developed by Frederick Sanger in the 1970s established genomics as the basis of comparative genetics. The recent invention of next-generation sequencing (NGS) platform has added a new dimension to genome research by generating ultra-fast and high-throughput sequencing data in an unprecedented manner. The advent of NGS technology also provides the opportunity to study genetic diseases where sequence variants or mutations are sought to establish a causal relationship with disease phenotypes. However, it is not a trivial task to seek genetic variants responsible for genetic diseases and even harder for complex diseases such as diabetes and cancers. In such polygenic diseases, multiple genes and alleles, which can exist in healthy individuals, come together to contribute to common disease phenotypes in a complex manner. Hence, it is desirable to have an approach that integrates omics data with both knowledge of protein structure and function and an understanding of networks/pathways, i.e. functional genomics and systems biology; in this way, genotype–phenotype relationships can be better understood. In this review, we bring this ‘bottom-up’ approach alongside the current NGS-driven genetic study of genetic variations and disease aetiology. We describe experimental and computational techniques for assessing genetic variants and their deleterious effects on protein structure and function.

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Notes

  1. http://www.genome.gov/gwastudies/.

  2. http://www.wtccc.org.uk/.

  3. http://www.genome.gov/10005107.

  4. http://www.1000genomes.org.

  5. http://www-cryst.bioc.cam.ac.uk/∼sdm/sdm.php.

  6. http://www.bongo.cl.cam.ac.uk/Bongo/.

  7. http://www-cryst.bioc.cam.ac.uk/samul (or http://samul.org, alternatively).

  8. http://www.dasregistry.org/.

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Acknowledgement

We are grateful to all who are developing and maintaining biological databases, scientists submitting their invaluable data and people who support open-source programmes and operating systems. SG, CLW and TC want to thank the Blundell Group members for their support and collaborations during their stay in Cambridge.

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Authors and Affiliations

  1. Biocomputing Group, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK

    Sungsam Gong, Catherine L. Worth, Tammy M. K. Cheng & Tom L. Blundell

  2. Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

    Sungsam Gong

  3. Charité Universitätsmedizin Berlin, Lindenberger Weg 80, 13125, Berlin, Germany

    Catherine L. Worth

  4. Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London, WC2A 3LY, UK

    Tammy M. K. Cheng

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  1. Sungsam Gong
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  2. Catherine L. Worth
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  4. Tom L. Blundell
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Correspondence to Sungsam Gong.

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Gong, S., Worth, C.L., Cheng, T.M.K. et al. Meet Me Halfway: When Genomics Meets Structural Bioinformatics. J. of Cardiovasc. Trans. Res. 4, 281–303 (2011). https://doi.org/10.1007/s12265-011-9259-1

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