Tuesday, 20. August 2019, 14.15 p.m. 

Ernst-Abbe-Platz 2, Seminarraum 3423

A network perspective on biologically-relevant chemical spaces

Prof. Dr. Areejit Samal (IMSc, Chennai, India)

In this talk, I will present our effort towards compilation, curation and network-based exploration of two biologically-relevant chemical spaces, namely, the phytoconstituents of Indian medicinal plants [1] and endocrine disrupting chemicals (EDCs) [2] in our environment.

In the first half of this talk, I will present our large-scale effort to map the phytochemical space of Indian medicinal plants. This effort has led to IMPPAT which is the largest digital database on phytoconstituents of Indian medicinal plants and provides a extensive chemical space for drug discovery [1]. IMPPAT encompasses 1742 Indian Medicinal Plants, 9596 Phytochemicals, And 1124 Therapeutic uses spanning 27074 plant-phytochemical associations and 11514 plant-therapeutic associations. Notably, we have filtered a subset of 960 drug-like phytochemicals, of which majority have no significant similarity to existing FDA approved drugs. We also 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. A comparison of phytochemicals from Indian medicinal plants in our resource with a large resource on phytochemicals from Chinese medicinal plants finds that majority of IMPPAT phytochemicals are unique to our resource. In sum, this work provides a new perspective on traditional Indian medicine through the interdisciplinary lens of computational biology.

In the second half of this talk, I will present our work on EDCs [2], which are a group of chemicals of emerging concern that are present in our everyday environment, and are known to cause adverse effects by interfering with the endocrine system. There is growing interest in unraveling the molecular mechanisms via which EDCs perturb the endocrine system. In this direction, we have developed a unique resource on EDCs that can facilitate the systems-level understanding of adverse effects upon EDC exposure. Specifically, using a detailed workflow with 4 stages, we have identified 686 potential EDCs along with their adverse effects by manual curation of ~16000 published research articles [2]. Subsequently, we have classified the EDCs based on the type of supporting evidence, environmental source or chemical properties. Moreover, for each EDC, we have compiled the endocrine-mediated adverse effects spanning across 7 systems-level perturbations. The compiled information on EDCs was used to create a community resource DEDuCT. Subsequent analysis based on the similarity of chemical structure and target genes of EDCs revealed a lack of correlation between structure and targets of EDCs. In sum, our work highlights the potential challenges in developing predictive models for adverse effects of EDCs.

References:
1. K. Mohanraj et al, Scientific Reports, 8: 4329 (2018).
2. B.S. Karthikeyan et al, Science of the Total Environment, 692: 281-296 (2019).