Dataset Information

?-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites.

ABSTRACT: Summary: Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene therapy or virally infected patients, essential for monitoring the evolution of genetically modified cells in vivo. However, since ?30% of insertions land in low complexity or repetitive regions of the host cell genome, they cannot be correctly assigned and are currently discarded, limiting the accuracy and predictive power of clonal tracking studies. Here, we present ?-TRIS, a new graph-based genome-free alignment tool for identifying insertion sites even if embedded in low complexity regions. By using ?-TRIS to reanalyze clinical studies, we observed improvements in clonal quantification and tracking.

Availability and implementation: Source code at https://bitbucket.org/bereste/g-tris.

Supplementary information: Supplementary data are available at Bioinformatics online.

SUBMITTER: Calabria A

PROVIDER: S-EPMC7703754 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites.

Calabria Andrea A Beretta Stefano S Merelli Ivan I Spinozzi Giulio G Brasca Stefano S Pirola Yuri Y Benedicenti Fabrizio F Tenderini Erika E Bonizzoni Paola P Milanesi Luciano L Montini Eugenio E

Bioinformatics (Oxford, England) 20200301 5

<h4>Summary</h4>Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene therapy or virally infected patients, essential for monitoring the evolution of genetically modified cells in vivo. However, since ∼30% of insertions land in low complexity or repetitive regions o ...[more]

PMID: 31589304

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Project description:BackgroundCarboxylation is a modification of glutamate (Glu) residues which occurs post-translation that is catalyzed by γ-glutamyl carboxylase in the lumen of the endoplasmic reticulum. Vitamin K is a critical co-factor in the post-translational conversion of Glu residues to γ-carboxyglutamate (Gla) residues. It has been shown that the process of carboxylation is involved in the blood clotting cascade, bone growth, and extraosseous calcification. However, studies in this field have been limited by the difficulty of experimentally studying substrate site specificity in γ-glutamyl carboxylation. In silico investigations have the potential for characterizing carboxylated sites before experiments are carried out.ResultsBecause of the importance of γ-glutamyl carboxylation in biological mechanisms, this study investigates the substrate site specificity in carboxylation sites. It considers not only the composition of amino acids that surround carboxylation sites, but also the structural characteristics of these sites, including secondary structure and solvent-accessible surface area (ASA). The explored features are used to establish a predictive model for differentiating between carboxylation sites and non-carboxylation sites. A support vector machine (SVM) is employed to establish a predictive model with various features. A five-fold cross-validation evaluation reveals that the SVM model, trained with the combined features of positional weighted matrix (PWM), amino acid composition (AAC), and ASA, yields the highest accuracy (0.892). Furthermore, an independent testing set is constructed to evaluate whether the predictive model is over-fitted to the training set.ConclusionsIndependent testing data that did not undergo the cross-validation process shows that the proposed model can differentiate between carboxylation sites and non-carboxylation sites. This investigation is the first to study carboxylation sites and to develop a system for identifying them. The proposed method is a practical means of preliminary analysis and greatly diminishes the total number of potential carboxylation sites requiring further experimental confirmation.

Dataset Information

?-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites.

Publications

γ-TRIS: a graph-algorithm for comprehensive identification of vector genomic insertion sites.

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