Network biology approach to human tissue-specific chemical exposome.

Human exposure to environmental chemicals is a major contributor to the global disease burden. To characterize the external exposome it is important to assess its chemical components and to study their impact on human health. Biomonitoring studies measure the body burden of environmental chemicals detected in biospecimens from a wide range of the population. The detection of these chemicals in biospecimens (and, hence, human tissues) is considered an important biomarker of human exposure. However, there is no readily available resource that compiles such exposure data for human tissues from published literature, and no studies that explore the patterns in the associations between tissue-specific exposures and human diseases. We present Human Tissue-specific Exposome Atlas (TExAs), a compilation of 380 environmental chemicals detected across 27 human tissues. TExAs is accessible via a user friendly webserver: https://cb.imsc.res.in/texas. We compare the chemicals in TExAs with 55 global chemical regulations, guidelines, and inventories, which represent several categories of the external exposome of humans. Further to understand the potential implications on human health of chemicals detected across human tissues, we employ a network biology approach and explore possible chemical exposure-disease associations. Ensuing analyses reveal the possibilities of disease comorbidities and demonstrate the application of network biology in unraveling complex disease associations due to chemical exposure.

NeurotoxKb 1.0: 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 1.0, 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 1.0 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 1.0 is accessible online at: https://cb.imsc.res.in/neurotoxkb/.

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

Human milk is a vital source of nourishment for infants. However, numerous environmental contaminants also find their way into human milk, making up the major part of a newborn's external exposome. While there are chemical regulations in India and scientific literature on environmental contaminants is available, the systematic compilation, monitoring, and risk management of human milk contaminants are inadequate. We have harnessed the potential of this large body of literature to develop the Exposome of Human Milk across India (ExHuMId) version 1.0 containing detailed information on 101 environmental contaminants detected in human milk samples 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. 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. Lastly, 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 1.0 is accessible online at: https://cb.imsc.res.in/exhumid/.

DEDuCT 2.0: An updated knowledgebase and an exploration of the current regulations and guidelines from the perspective of endocrine disrupting chemicals.

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.

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

Phytochemicals of medicinal plants encompass a diverse chemical space for drug discovery. 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 computational approaches towards natural product based drug discovery. In this direction, we present, IMPPAT, a manually curated database of 1742 Indian Medicinal Plants, 9596 Phytochemicals, And 1124 Therapeutic uses spanning 27074 plant-phytochemical associations and 11514 plant-therapeutic associations. Notably, the curation effort led to a non-redundant in silico library of 9596 phytochemicals with standard chemical identifiers and structure information. Using cheminformatic approaches, we have computed the physicochemical, ADMET (absorption, distribution, metabolism, excretion, toxicity) and drug-likeliness properties of the IMPPAT phytochemicals. We show that the stereochemical complexity and shape complexity of IMPPAT phytochemicals differ from libraries of commercial compounds or diversity-oriented synthesis compounds while being similar to other libraries of natural products. Within IMPPAT, we have filtered a subset of 960 potential druggable phytochemicals, of which majority have no significant similarity to existing FDA approved drugs, and thus, rendering them as good candidates for prospective drugs. IMPPAT database is openly accessible at: https://cb.imsc.res.in/imppat .