Biology subjects

Karthikeyan, B. S.

Publications and source records attributed to Karthikeyan, B. S..

7 recordsLinked to original sources

bioRxiv2024

UVREK: Development and analysis of an expression profile knowledgebase of biomolecules induced by ultraviolet radiation exposure

Humans encounter diverse environmental factors which can have impact on their health. One such environmental factor is the ultraviolet (UV) radiation, which is part of the physical component of the exposome. UV radiation is the leading cause of skin cancer and is a significant global health concern. A large body of published research has been conducted to uncover the mechanisms underlying the adverse outcomes of UV radiation exposure on living beings. These studies involve identifying the biomolecules induced upon UV radiation exposure. A few previous efforts have attempted to compile this information in the form of a database, but such earlier efforts have certain limitations. To fill this gap, we present a structured database named UVREK, containing manually curated data on biomolecules induced by UV radiation exposure from published literature. UVREK has compiled information on 985 genes, 470 proteins, 54 metabolites and 77 miRNAs along with their metadata. Thereafter, an enrichment analysis performed on the human gene set of UVREK database showed the importance of transcription related processes in UV related response, and enrichment of pathways involved in cancer and aging. While significantly contributing towards characterizing the physical component of the exposome, we expect the compiled data in UVREK will serve as a valuable resource for development of better UV protection mechanisms such as UV sensors and sunscreens. Noteworthy, UVREK is the only resource to date, compiling varied types of biomolecular responses to UV radiation with corresponding metadata. UVREK is openly accessible at: https://cb.imsc.res.in/uvrek/.

bioinformatics↗

bioRxiv2021

Investigation of a derived adverse outcome pathway (AOP) network for endocrine-mediated perturbations

An adverse outcome pathway (AOP) is a compact representation of the available mechanistic information on observed adverse effects upon environmental exposure. Sharing of events across individual AOPs has led to the emergence of AOP networks. Since AOP networks are expected to be functional units of toxicity prediction, there is current interest in their development tailored to specific research question or regulatory problem. To this end, we have developed a detailed workflow to construct a comprehensive endocrine-specific AOP (ED-AOP) network. Connectivity analysis of the ED-AOP network comprising 48 AOPs reveals 7 connected components and 12 isolated AOPs. Subsequently, we apply standard network measures to perform an in-depth analysis of the two largest connected components of the ED-AOP network. Notably, the graph-theoretic analyses led to the identification of important events including points of convergence or divergence in the ED-AOP network. Detailed analysis of the largest component in the ED-AOP network gives insights on the systems-level perturbations caused by endocrine disruption, emergent paths, and stressor-event associations. In sum, the derived ED-AOP network can be used to address the current knowledge gaps in the existing regulatory framework and aid in better risk assessment of environmental chemicals.

pharmacology and toxicology↗

bioRxiv2021

NeurotoxKb: compilation, curation and exploration of a knowledgebase of environmental neurotoxicants specific to mammals

Exposure to environmental neurotoxicants is a significant concern due to their potential to cause permanent or irreversible damage to the human nervous system. Here, we present the first dedicated knowledgebase, NeurotoxKb, on environmental neurotoxicants specific to mammals. Using a detailed workflow, we have compiled 475 potential non-biogenic neurotoxicants from 835 published studies with evidence of neurotoxicity specific to mammals. A unique feature of NeurotoxKb is the manual curation effort to compile and standardize the observed neurotoxic effects for the potential neurotoxicants from 835 published studies. For the 475 potential neurotoxicants, we have compiled diverse information such as chemical structures, environmental sources, chemical classification, physicochemical properties, molecular descriptors, predicted ADMET properties, and target human genes. To better understand the prospect of human exposure, we have explored the presence of potential neurotoxicants in external exposomes via two different analyses. By analyzing 55 chemical lists representing global regulations and guidelines, we reveal potential neurotoxicants both in regular use and produced in high volume. By analyzing human biospecimens, we reveal potential neurotoxicants detected in them. Lastly, a construction of the chemical similarity network and ensuing analysis revealed the diversity of the toxicological space of 475 potential neurotoxicants. NeurotoxKb is accessible online at: https://cb.imsc.res.in/neurotoxkb/.

pharmacology and toxicology↗

bioRxiv2020

ExHuMId: A curated resource and analysis of Exposome of Human Milk across India

Human milk is a vital source of nourishment for infants, containing nutrients, immunoprotective components, and bioactive substances. However, several environmental contaminants find their way into human milk. Although lactation physiology has been well documented, the effect of human milk contaminants on maternal and infant health remains unclear. Human milk is the major route of contaminant exposure to infants; these contaminants and their effects can themselves be considered an exposome. While there are chemical regulations in India and scientific literature on environmental contaminants is available, yet there is a lack of systematic compilation, monitoring, and risk management of human milk contaminants. We have harnessed the potential of this large body of literature to develop the Exposome of Human Milk across India (ExHuMId) containing detailed information on 101 environmental contaminants detected in human milk samples, studied across 13 Indian states, compiled from 36 research articles. ExHuMId also compiles the detected concentrations of the contaminants, structural and physicochemical properties, and factors associated with the donor of the sample. Here, we also present findings from a three-pronged analysis of ExHuMId and two other resources on human milk contaminants, with a focus on the Indian scenario. Through a comparative analysis with global chemical regulations and guidelines, we identify human milk contaminants of high concern, such as potential carcinogens, endocrine disruptors and neurotoxins. We then study the physicochemical properties of the contaminants to gain insights on their propensity to transfer into human milk. Further, we employ a systems biology approach to shed light on potential effects of human milk contaminants on maternal and infant health, by identifying contaminant-gene interactions associated with lactation, cytokine signalling and production, and protein-mediated transport. ExHuMId is accessible online at: https://cb.imsc.res.in/exhumid/.

pharmacology and toxicology↗

bioRxiv2020

An exploratory analysis of the current chemical regulations and guidelines from the perspective of endocrine disrupting chemicals using public resources

The regulatory assessment of endocrine disrupting chemicals (EDCs) is complex due to the lack of a standardized definition of EDCs and validated testing criteria. In spite of these challenges, there is growing scientific interest in EDCs which has resulted in the rapid expansion of published literature on endocrine disruption upon chemical exposure. Here, we explore how academic research leading to curated knowledgebases can inform current chemical regulations on EDCs. To this end, we present an updated knowledgebase, DEDuCT 2.0, containing 792 potential EDCs with supporting evidence from 2218 research articles. Thereafter, we study the distribution of potential EDCs across several chemical lists that reflect guidelines for use or regulations. Further, to understand the scale of possible exposure to the potential EDCs present in chemical lists, we compare them with high production volume chemicals. Notably, we find many potential EDCs are in use across various product categories such as Food additives and Food contact materials and Cosmetics and household products. Several of these EDCs are also produced or manufactured in high volume across the world. Lastly, we illustrate using an example how diverse information in curated knowledgebases such as DEDuCT 2.0 can be helpful in the risk assessment of EDCs. In sum, we highlight the need to bridge the gap between academic and regulatory aspects of chemical safety, as a step towards the better management of environment and health hazards such as EDCs.

pharmacology and toxicology↗

bioRxiv2019

A curated knowledgebase enabling a network perspective on endocrine disrupting chemicals and their biological systems-level perturbations

Human well-being can be affected by exposure to several chemicals in the environment. One such group is endocrine disrupting chemicals (EDCs) that can perturb the hormonal homeostasis leading to adverse health effects. In this work, we have developed a detailed workflow to identify EDCs with supporting evidence of endocrine disruption in published experiments in humans or rodents. Thereafter, this workflow was used to manually evaluate more than 16000 published research articles and identify 686 potential EDCs with published evidence in humans or rodents. Importantly, we have compiled the observed adverse effects or endocrine-specific perturbations along with the dosage information for the potential EDCs from their supporting published experiments. Subsequently, the potential EDCs were classified based on the type of supporting evidence, their environmental source and their chemical properties. Additional compiled information for potential EDCs include their chemical structure, physicochemical properties, predicted ADMET properties and target genes. In order to enable future research based on this compiled information on potential EDCs, we have built an online knowledgebase, Database of Endocrine Disrupting Chemicals and their Toxicity profiles (DEDuCT), accessible at: https://cb.imsc.res.in/deduct/. After building this comprehensive resource, we employed a network biology approach to study the chemical space of EDCs and its potential link to the biological space of target genes of EDCs. Specifically, we have constructed two networks of EDCs using our resource based on similarity of chemical structures or target genes. Ensuing analysis of these two networks revealed that EDCs can differ both in their chemical structure and set of target genes. Though our detailed results highlight potential challenges in developing predictive models for EDCs, the compiled information in our resource will undoubtedly enable future research in the field, especially, those focussed towards mechanistic understanding of the systems-level perturbations caused by EDCs.

bioinformatics↗

bioRxiv2017

IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry And Therapeutics

Phytochemical constituents of medicinal plants encompass a diverse space of chemical scaffolds which can be used for rational design of novel drugs. India is rich with a flora of indigenous medicinal plants that have been used for centuries in traditional Indian medicine to treat human maladies. A comprehensive online database on the phytochemistry of Indian medicinal plants will enable the application of systems biology and cheminformatic approaches towards natural product based drug discovery. In this direction, we here present, IMPPAT, a manually curated database of Indian Medicinal Plants, Phytochemistry, And Therapeutics. IMPPAT contains 1742 Indian medicinal plants, 9596 phytochemicals and 1124 therapeutic uses which span across 27074 plant-phytochemical associations and 11514 plant-therapeutic associations. Notably, the curation effort led to a non-redundant in silico chemical library of 9596 phytochemicals with standard chemical identifiers and structure information. Using cheminformatic approaches, we have computed the physicochemical properties and drug-likeliness of the phytochemicals in IMPPAT which led to a filtered subset of 960 potential druggable phytochemicals. Moreover, a comparative analysis against FDA approved drugs suggests that majority of the druggable phytochemicals in IMPPAT are good candidates for novel prospective drugs as they have little or no structural similarity with existing drugs. The IMPPAT database is openly accessible at: https://www.imsc.res.in/~asamal/resources/imppat/home.

bioinformatics↗