DMDtoolkit: a tool for visualizing the mutated dystrophin protein and predicting the clinical severity in DMD

Abstract

BackgroundDystrophinopathy is one of the most common human monogenic diseases which results in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Mutations in the dystrophin gene are responsible for both DMD and BMD. However, the clinical phenotypes and treatments are quite different in these two muscular dystrophies. Since early diagnosis and treatment results in better clinical outcome in DMD it is essential to establish accurate early diagnosis of DMD to allow efficient management. Previously, the reading-frame rule was used to predict DMD versus BMD. However, there are limitations using this traditional tool. Here, we report a novel molecular method to improve the accuracy of predicting clinical phenotypes in dystrophinopathy. We utilized several additional molecular genetic rules or patterns such as “ambush hypothesis”, “hidden stop codons” and “exonic splicing enhancer (ESE)” to predict the expressed clinical phenotypes as DMD versus BMD.ResultsA computer software “DMDtoolkit” was developed to visualize the structure and to predict the functional changes of mutated dystrophin protein. It also assists statistical prediction for clinical phenotypes. Using the DMDtoolkit we showed that the accuracy of predicting DMD versus BMD raised about 3% in all types of dystrophin mutations when compared with previous methods. We performed statistical analyses using correlation coefficients, regression coefficients, pedigree graphs, histograms, scatter plots with trend lines, and stem and leaf plots.ConclusionsWe present a novel DMDtoolkit, to improve the accuracy of clinical diagnosis for DMD/BMD. This computer program allows automatic and comprehensive identification of clinical risk and allowing them the benefit of early medication treatments. DMDtoolkit is implemented in Perl and R under the GNU license. This resource is freely available at http://github.com/zhoujp111/DMDtoolkit, and http://www.dmd-registry.com.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-017-1504-4) contains supplementary material, which is available to authorized users.

Comprehensive genetic characteristics of dystrophinopathies in China

“…Computer software called “DMD toolkit” was developed to visualize the structure of DMD and to predict the functional changes of mutated dystrophin protein. In addition, the software helps improve the accuracy of clinical diagnosis [ 10 ].…”

Quel avenir pour la dystrophine ?

“…L'efficacité des inhibiteurs de l'enzyme de conversion (IEC) sur le déve-loppement de la cardiomyopathie est également bien documentée [54]. D'autres thérapeutiques ou supplémentations diététiques font encore l'objet de recherche [55][56][57][58][59][60][61]. Il semble donc que l'on s'achemine vers des théra-peutiques plurielles qui pourraient être associées, de manière plus ou moins personnalisée, en fonction des données génétiques et cliniques.…”

LncRNA HOXA-AS2 Promotes Oral Squamous Cell Proliferation, Migration, and Invasion via Upregulating EZH2 as an Oncogene

“… 17 With the development of genomics, a set of lncRNAs with more than 200 nt is abnormally expressed in a variety of tumor cells, where they have been found to play important roles in regulating the biological behavior of tumor cells including proliferation, invasion, and metastasis. 18 , 19 Therefore, the in-depth investigations of lncRNAs may help to provide novel treatment strategies for OSCC. As a subset of lncRNAs, HOXA-AS2 fulfills a carcinogenic role in many kinds of cancers.…”