DMDM: domain mapping of disease mutations

Peterson, Thomas; Adadey, Asa; Santana-Cruz, Ivette; Sun, Yanyu; Winder, A; Kann, Maricel G.

doi:10.1093/bioinformatics/btq447

Cited by 56 publications

(49 citation statements)

References 18 publications

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“…The resulting PCR products were then subjected to direct sequencing using the same primers, and all variants were confirmed by sequences originating from both upstream and downstream primers. Of the patients analyzed, 210 exhibited nonsynonymous sequence variants in the sequenced exons that were checked in COSMIC (Forbes et al, 2011), Humsavar (Humsavar Database, Geneva, Switzerland: Swiss Institute of Bioinformatics, http://www.uniprot.org/docs/humsavar), ClinVar (ClinVar database, Release weekly,Bethesda, MD, USA: National Center for Biotechnology Information, US, National Library of Medicine, (http://www.ncbi.nlm.nih.gov/clinvar/), DMDM (Peterson et al, 2010) and bibliographic databases to verify previous reports. To evaluate whether these variants involved structural and/or functionally relevant positions, the structures of different conformers were extracted from the CoDNas database (Monzon et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

Untitled

2015

Annals of Human Genetics

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SummarySomatic sequence variants in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with nonsmall cell lung cancer (NSCLC). Patients exhibiting sequence variants in this domain that produce kinase activity enhancement, are more likely to benefit from TKIs than patients with EGFR wild-type disease. Although most NSCLC EGFR-related alleles are concentrated in a few positions, established protocols recommend sequencing EGFR exons 18-21. In this study, 21 novel somatic variants belonging to such exons in adult Argentinean patients affected with NSCLC are reported. Of these, 18 were single amino acid substitutions (SASs), occurring alone or in combination with another genetic alteration (complex cases), one was a short deletion, one was a short deletion-short insertion combination, and one was a duplication. New variants and different combinations of previously reported variants were also found. Moreover, two of the reported SASs occurred in previously unreported positions of the EGFR kinase domain. In order to characterize the new sequence variants, physicochemical, sequence and conformational analyses were also performed. A better understanding of sequence variants in NSCLC may facilitate the most appropriate treatment choice for this complex disease.

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Section: Methodsmentioning

confidence: 99%

Untitled

2015

Annals of Human Genetics

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“…Proteome-wide analyses have been performed to identify domains enriched in missense mutations [45,47] [50] and to identify domain-centric positions of hotspot missense mutations [48,49] [50]. These studies focused exclusively on missense mutation and as yet, little attempt was to use these data to distinguish between activating and loss of function mutations in the majority of cases.…”

Section: Domain-based Approaches At Identifying Mutational Hotspotsmentioning

confidence: 99%

Mutational patterns in oncogenes and tumour suppressors

Baeissa

Benstead-Hume

Richardson

et al. 2016

Biochemical Society Transactions

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All cancers depend upon mutations in critical genes, which confer a selective advantage to the tumour cell. Knowledge of these mutations is crucial to understanding the biology of cancer initiation and progression, and to the development of targeted therapeutic strategies. The key to understanding the contribution of a disease-associated mutation to the development and progression of cancer, comes from an understanding of the consequences of that mutation on the function of the affected protein, and the impact on the pathways in which that protein is involved.In this paper we examine the mutation patterns observed in oncogenes and tumour suppressors, and discuss different approaches that have been developed to identify driver mutations within cancers that contribute to the disease progress. We also discuss the MOKCa database where we have developed an automatic pipeline that structurally and functionally annotates all proteins from the human proteome that are mutated in cancer.

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“…3A, 3B) confirmed that both cystatin SN protein species (27 and 34) were not phosphorylated. At least three polymorphisms involving a variation in pI have been reported for cystatin SN: N 129 -N D, R 131 -N M, K 135 -N N [42]. By analyzing the MS/MS spectra of the tryptic peptides obtained from spots 27 and 34, it was possible to exclude the presence of the substitution at position 129, but not the substitutions at position 131 and 135.…”

Section: Other Secreted Proteinsmentioning

confidence: 99%