Data Mining for Drug Repurposing and New Targets Identification for Radioprotection

Ionising radiation (IR) is responsible for various types of tissue injury leading to morbidity at low doses and mortality at high radiation exposure. Although many radioprotective and pharmacological agents are being tested for decreasing radiation injury, however, the availability of Amifostine as the only clinically used radioprotector with limited indication has prompted us to find out new potential molecules through drugs repurposing for protecting or decreasing radiation damage by data mining. In this work we have used text-mining based network generation approach to find out the gene targets of radioprotectors under evaluation by Agilent Literature Search app in Cytoscape. Extracted genes were evaluated for their association with radiation in Radiation Genes database. These genes were searched against therapeutic drugs and molecules under clinical trial in the Drug Gene Interaction database. We found that most of the radiation target genes were involved in cell death, proliferation, homeostasis, cell cycle and cancer pathways. Many of these genes were druggable and could be targeted by the drugs under clinical research, whereas there were few genes (new targets), which were never considered for radioprotective drug development. This study would likely help in repurposing of identified drugs for use in the event of radiation fallout, keeping in mind that no radiation medical countermeasure for acute radiation syndrome has been approved by the US FDA for use in humans. Results also revealed new target genes for drug targeting and indicates use of similar pipeline in other pathologies for drug repurposing and development

A Hypothetical Tool for Integrated Omics, Drugs and Clinical Stem Cell Data Analysis

Understanding the molecular basis of stem cell (SC) function is essential to regenerate damaged tissue due to various types of injuries and pathologies. However, there are bottlenecks that prevent the use of Stem cell in the treatment of wide range of diseases. Complete information regarding the control of gene expression in Stem cell is necessary to understand the regulation of Stem cell fates such as self-renewal, differentiation, migration/ homing and apoptosis. However, in the absence of multi-functional, single window tool for the analysis of various omics and drugs data related to Stem cell, the knowledge consolidation is missing to fully harness its potential. A tool which can integrate various databases, analysis software and gives a probable solution for Stem cell mediated regeneration of tissues using available therapeutic options would likely to help in reducing morbidity and mortality associated with various pathologies. This subsumes omics based repurposing of drugs for Stem cell guided tissue regeneration, which will be a boon for clinicians to treat various debilitating diseases/ malfunctions

AbODE: Ab Initio Antibody Design using Conjoined ODEs

Antibodies are Y-shaped proteins that neutralize pathogens and constitute the core of our adaptive immune system. De novo generation of new antibodies that target specific antigens holds the key to accelerating vaccine discovery. However, this co-design of the amino acid sequence and the 3D structure subsumes and accentuates some central challenges from multiple tasks, including protein folding (sequence to structure), inverse folding (structure to sequence), and docking (binding). We strive to surmount these challenges with a new generative model AbODE that extends graph PDEs to accommodate both contextual information and external interactions. Unlike existing approaches, AbODE uses a single round of full-shot decoding and elicits continuous differential attention that encapsulates and evolves with latent interactions within the antibody as well as those involving the antigen. We unravel fundamental connections between AbODE and temporal networks as well as graph-matching networks. The proposed model significantly outperforms existing methods on standard metrics across benchmarks.Comment: Accepted at ICML 202

Comparative genetic diversity analysis of oat (Avena sativa L.) by microsatellite markers and morphological rainfed expressions

Equivalence was appraised between phenotypic and molecular markers (ISSR) to analyze the genetic diversity of 20 high yielding genotypes representing different geographical zones of the world. A moderate range of genetic similarity (0.84 to 0.20) was observed on the basis of 20 inter-simple sequence repeats (ISSR) markers, where it was found high (0.995 – 0.204) on the basis of 7 primary morphological rainfed expression. Genotypes in morphological character based dendogram were clustered into their respective geographic groups, while a random grouping was observed in dendogram based on the ISSR markers. A negative correlation (r = -0.186) was found among morphological and molecular marker systems, but the latter was found effective in distinguishing the genotypes using specific band positions for them. The genotypic classification agreed closely with the grouping observed in ISSR based 3D analysis.Keywords: Avena sativa, diversity, inter-simple sequence repeats (ISSR), morphology, oat, relationshipAfrican Journal of Biotechnology Vol. 12(22), pp. 3414-342

Comparative study between various reduced model and modal analysis of viscoelastic rotors

The present work includes the study of dynamic characteristics on a flexible rotor shaft system. This arises due to the internal material damping of rotor bearing system, which produces a tangential force on a rotor and increasing with the rotor spin speed. Due to these dynamic characteristics of rotor is influence which destabilizes the rotor shaft system. Under this dynamic behaviour of rotor shaft system is studied to get the dynamic nature of rotor shaft system. This can be estimated in terms of Campbell diagram, modal damping factor, mode shape and directional frequency response function. These plots are obtained by using the matlab software by solving a eigenvalues problem. finite element approach plays a significant role in modelling continuum system after discretizing it into some finite number of element. More number of elements or enhancing the mesh size give better accuracy in results. But discretizing the system into infinite elements inherits the swelling size of system matrices. Substantial increment of the system matrices sometime causes very high mathematical complications and takes an unwanted computational time. Model reduction is techniques for reducing the degree of freedom from the full system model to produce a reduced model but its dynamic characteristics is maintain. System equivalent reduction process, Improved reduced system, Guyan reduction are used to reduce the large system of equation of motion to fewer degree of freedom. The full system model also includes internal and external damping and gyroscopic effect. Since it is not practical to measure all degree of freedom, so the model is reduced using model reduction techniques. The reduced model is used to plot Campbell diagram, unbalance response using MATLAB software and comparison is done with original system to show its effectiveness