Modelling Intermolecular Structures and Defining Ambiguity in Gene Sequences using Matrix Insertion-Deletion Systems

International audienceGene insertion and deletion are considered as the basic operations in DNA processing and RNA editing. Based on these evolutionary transformations, a computing model has been formulated in formal language theory known as insertion-deletion systems. Recently, in [6], a new computing model named Matrix insertion-deletion system has been introduced to model various bio-molecular structures such as hairpin, stem and loop, pseudoknot, attenuator, cloverleaf, dumbbell that occur at intramolecular level. In this paper, we model some of the intermolecular structures such as double strand languages, nick languages, hybrid molecules (with R-loops), holliday structure, replication fork and linear hybridization (ligated) languages using Matrix insertion-deletion system. In [2], the ambiguity in gene sequence was defined as deriving more than one structure for a single gene sequence. Here, we propose a different view of understanding the ambiguity in gene sequences: A gene sequence is obtained by more than one way such that their intermediate sequences are different. We further classify the ambiguity into many levels based on the components axiom, string (order of deletion/insertion) and contexts (order of the used contexts). We notice that some of the inter and intramolecular structures obey the newly defined ambiguity levels.L'insertion et l'effacement de gènes sont considérés comme les opérations de base dans le traitement de l'ADN et l'édition de l'ARN. Fondé sur ces méchanismes de l'évolution, un modèle de calcul a été formulé dans le cadre de la théorie des langages formels en tant que système d'ajout-effacement. Récemment, un nouveau modèle dénommé "système matriciel d'ajout-effacement" a été introduit pour modéliser différentes structures bio-moléculaires qui apparaissent au niveau intra-moléculaire. Dans ce papier, nous modélisons certaines de ces structures

Modelling Intermolecular Structures and Defining Ambiguity in Gene Sequences using Matrix Insertion-Deletion Systems

International audienceGene insertion and deletion are considered as the basic operations in DNA processing and RNA editing. Based on these evolutionary transformations, a computing model has been formulated in formal language theory known as insertion-deletion systems. Recently, in [6], a new computing model named Matrix insertion-deletion system has been introduced to model various bio-molecular structures such as hairpin, stem and loop, pseudoknot, attenuator, cloverleaf, dumbbell that occur at intramolecular level. In this paper, we model some of the intermolecular structures such as double strand languages, nick languages, hybrid molecules (with R-loops), holliday structure, replication fork and linear hybridization (ligated) languages using Matrix insertion-deletion system. In [2], the ambiguity in gene sequence was defined as deriving more than one structure for a single gene sequence. Here, we propose a different view of understanding the ambiguity in gene sequences: A gene sequence is obtained by more than one way such that their intermediate sequences are different. We further classify the ambiguity into many levels based on the components axiom, string (order of deletion/insertion) and contexts (order of the used contexts). We notice that some of the inter and intramolecular structures obey the newly defined ambiguity levels.L'insertion et l'effacement de gènes sont considérés comme les opérations de base dans le traitement de l'ADN et l'édition de l'ARN. Fondé sur ces méchanismes de l'évolution, un modèle de calcul a été formulé dans le cadre de la théorie des langages formels en tant que système d'ajout-effacement. Récemment, un nouveau modèle dénommé "système matriciel d'ajout-effacement" a été introduit pour modéliser différentes structures bio-moléculaires qui apparaissent au niveau intra-moléculaire. Dans ce papier, nous modélisons certaines de ces structures

The stability and activity of human neuroserpin are modulated by a salt bridge that stabilises the reactive centre loop

Neuroserpin (NS) is an inhibitory protein belonging to the serpin family and involved in several pathologies, including the dementia Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), a genetic neurodegenerative disease caused by accumulation of NS polymers. Our Molecular Dynamics simulations revealed the formation of a persistent salt bridge between Glu289 on strand s2C and Arg362 on the Reactive Centre Loop (RCL), a region important for the inhibitory activity of NS. Here, we validated this structural feature by simulating the Glu289Ala mutant, where the salt bridge is not present. Further, MD predictions were tested in vitro by purifying recombinant Glu289Ala NS from E. coli. The thermal and chemical stability along with the polymerisation propensity of both Wild Type and Glu289Ala NS were characterised by circular dichroism, emission spectroscopy and non-denaturant gel electrophoresis, respectively. The activity of both variants against the main target protease, tissue-type plasminogen activator (tPA), was assessed by SDS-PAGE and chromogenic kinetic assay. Our results showed that deletion of the salt bridge leads to a moderate but clear reduction of the overall protein stability and activity

Tenomodulin expression in the periodontal ligament enhances cellular adhesion.

Tenomodulin (Tnmd) is a type II transmembrane protein characteristically expressed in dense connective tissues such as tendons and ligaments. Its expression in the periodontal ligament (PDL) has also been demonstrated, though the timing and function remain unclear. We investigated the expression of Tnmd during murine tooth eruption and explored its biological functions in vitro. Tnmd expression was related to the time of eruption when occlusal force was transferred to the teeth and surrounding tissues. Tnmd overexpression enhanced cell adhesion in NIH3T3 and human PDL cells. In addition, Tnmd-knockout fibroblasts showed decreased cell adhesion. In the extracellular portions of Tnmd, the BRICHOS domain or CS region was found to be responsible for Tnmd-mediated enhancement of cell adhesion. These results suggest that Tnmd acts on the maturation or maintenance of the PDL by positively regulating cell adhesion via its BRICHOS domain

EPIC: Graph Augmentation with Edit Path Interpolation via Learnable Cost

Graph-based models have become increasingly important in various domains, but the limited size and diversity of existing graph datasets often limit their performance. To address this issue, we propose EPIC (Edit Path Interpolation via learnable Cost), a novel interpolation-based method for augmenting graph datasets. Our approach leverages graph edit distance to generate new graphs that are similar to the original ones but exhibit some variation in their structures. To achieve this, we learn the graph edit distance through a comparison of labeled graphs and utilize this knowledge to create graph edit paths between pairs of original graphs. With randomly sampled graphs from a graph edit path, we enrich the training set to enhance the generalization capability of classification models. We demonstrate the effectiveness of our approach on several benchmark datasets and show that it outperforms existing augmentation methods in graph classification tasks