Plot protein: visualization of mutations

Journal of Clinical Bioinformatics

Tychele Turner¹ 

[1] Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, MRB 572, Baltimore, MD 21205, USA

关键词: Plot;    Visualization;    Cluster;    Disease;    Mutation;    Protein;   

Others  :  802822
DOI  :  10.1186/2043-9113-3-14

 received in 2013-04-30, accepted in 2013-07-17,  发布年份 2013

【 摘 要 】

Background

Next-generation sequencing has enabled examination of variation at the DNA sequence level and can be further enhanced by evaluation of the variants at the protein level. One powerful method is to visualize these data often revealing patterns not immediately apparent in a text version of the same data. Many investigators are interested in knowing where their amino acid changes reside within a protein. Clustering of variation within a protein versus non-clustering can show interesting aspects of the biological changes happening in disease.

Finding

We describe a freely available tool, Plot Protein, executable from the command line or utilized as a graphical interface through a web browser, to enable visualization of amino acid changes at the protein level. This allows researchers to plot variation from their sequencing studies in a quick and uniform way. The features available include plotting amino acid changes, domains, post-translational modifications, reference sequence, conservation, conservation score, and also zoom capabilities. Herein we provide a case example using this tool to examine the RET protein and we demonstrate how clustering of mutations within the protein in Multiple Endocrine Neoplasia 2A (MEN2A) reveals important information about disease mechanism.

Conclusions

Plot Protein is a useful tool for investigating amino acid changes and their localization within proteins. Command line and web server versions of this software are described that enable users to derive visual knowledge about their mutations.

【 授权许可】

   
2013 Turner; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]The 1000 Genomes Project Consortium: A map of human genome variation from population-scale sequencing. Nature 2010, 467:1061-1073.
• [2]Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D: The human genome browser at UCSC. Genome Research 2002, 12:996-1006.
• [3]Charif D, Lobry JR: Seqinr 1.0-2: A Contributed Package to the {R} Project for Statistical Computing Devoted to Biological Sequences Retrieval and Analysis. Structural Approaches to Sequence Evolution: Molecules, Networks, Populations 2007, 207-232.
• [4]Edgar RC: MUSCLE: Multiple Sequence Alignment with High Accuracy and High Throughput. Nucleic Acids Res. 2004, 32:1792-1797.
• [5]Prasad TSK, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, Balakrishnan L, Marimuthu A, Banerjee S, Somanathan DS, Sebastian A, Rani S, Ray S, Harrys Kishore CJ, Kanth S, Ahmed M, Kashyap MK, Mohmood R, Ramachandra YL, Krishna V, Rahiman BA, Mohan S, Ranganathan P, Ramabadran S, Chaerkady R, Pandey A: Human Protein Reference Database–2009 update. Nucleic Acids Res. 2009, 37:D767-772.
• [6]Wagner SM, Zhu S, Nicolescu AC, Mulligan LM: Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2. Clinics 2012, 67:77-84.
• [7]Arlt DH, Baur B, Wagner B, Hoppner W: A novel type of mutation in the cysteine rich domain of the RET receptor causes ligand independent activation. Oncogene 2000, 19:3445-3448.
• [8]Kjaer S, Kurokawa K, Perrinjaquet M, Abrescia C, Ibanez CF: Self-association of the transmembrane domain of RET underlies oncogenic activation by MEN2A mutations. Oncogene 2006, 25:7086-7095.