Category: Algorithms and Tools

DeepOlf: Deep neural network based architecture for predicting odorants and their interacting Olfactory Receptors

Abstract:

Olfaction transduction mechanism is triggered by the binding of odorants to the specific olfactory receptors (OR’s) present in the nasal cavity. Different odorants stimulate different OR’s due to the difference in shape, physical and chemical properties. In this paper, a deep neural network architecture DeepOlf, based on molecular features and fingerprints of odorants and ORs, to predict whether a chemical compound is a potential odorant or not along with its interacting OR is proposed. Odorant identification and Odorant-OR interaction were modeled as a binary classification through multiple classifiers. The evaluation of these classifier’s performance showed that the deep-neural network framework not only fits data with better accuracy in comparison to other classical methods (SVM, RF, k-NN) but also able to predict odorant-OR interactions more accurately. To our knowledge, this study is the first realization of deep learning ideas for the problem of odorant and interacting OR prediction. The accuracy of DeepOlf was found to be 94.83% and 99.92 % for the prediction of odorants and Odorant- OR interactions respectively. Comparison of DeepOlf prediction with the existing SVM based prediction server, ODORactor, showed that better performance can be achieved with the proposed deep learning approach. The DeepOlf tool can be accessed at https://bioserver.iiita.ac.in/deepolf/.
Published in: IEEE/ACM Transactions on Computational Biology and Bioinformatics ( Early Access )
Date of Publication: 12 June 2020 

DeEPn: A deep neural network based tool for enzyme functional annotation

Authors: Rahul Semwal, Imlimaong Aier, Pankaj Tyagi, Pritish Kumar Varadwaj
With the advancement of high throughput techniques, the discovery rate of enzyme sequences has increased significantly in the recent past. All of these raw sequences are required to be precisely mapped to their respective functional attributes, which helps in deciphering their biological role. In the recent past, various prediction models have been proposed to predict the enzyme functional class; however, all of these models were able to quantify at most six functional enzyme classes (EC1 to EC6) out of existing seven functional classes, making these approaches inappropriate for handling enzymes corresponding to the seventh functional class (EC7). In this study, a Deep Neural Network-based approach, DeEPn, has been proposed, which can quantify enzymes corresponding to all seven functional classes with high precision and accuracy. The proposed model was compared with two recently developed tools, ECPred and SVM-Prot. The result demonstrated that DeEPn outperformed ECPred and SVM-Prot in terms of predictive quality. The DeEPn tool has been hosted as a web-based tool at https://bioserver.iiita.ac.in/DeEPn/.

Understanding the Mechanism of Cell Death in Gemcitabine Resistant Pancreatic Ductal Adenocarcinoma: A Systems Biology Approach

Background: Gemcitabine is the standard chemotherapeutic drug administered in advanced Pancreatic Ductal Adenocarcinoma (PDAC). However, due to drug resistance in PDAC patients, this treatment has become less effective. Over the years, clinical trials for the quest of finding novel compounds that can be used in combination with gemcitabine have met very little success.

Objective: To predict the driving factors behind pancreatic ductal adenocarcinoma, and to understand the effect of these components in the progression of the disease and their contribution to cell growth and proliferation.

Methods: With the help of systems biology approaches and using gene expression data, which is generally found in abundance, dysregulated elements in key signalling pathways were predicted. Prominent dysregulated elements were integrated into a model to simulate and study the effect of gemcitabine- induced hypoxia.

Results: In this study, several transcription factors in the form of key drivers of cancer-related genes were predicted with the help of CARNIVAL, and the effect of gemcitabine-induced hypoxia on the apoptosis pathway was shown to have an effect on the downstream elements of two primary pathway models; EGF/VEGF and TNF signalling pathway.

Conclusion: It was observed that EGF/VEGF signalling pathway played a major role in inducing drug resistance through cell growth, proliferation, and avoiding cell death. Targeting the major upstream components of this pathway could potentially lead to successful treatment.

Deciphering the Novel Target Genes Involved in the Epigenetics of Hepatocellular Carcinoma Using Graph Theory Approach

Background: Even after decades of research, cancer, by and large, remains a challenge and is one of the major causes of death worldwide. For a very long time, it was believed that cancer is simply an outcome of changes at the genetic level but today, it has become a well-established fact that both genetics and epigenetics work together resulting in the transformation of normal cells to cancerous cells.

Objective: In the present scenario, researchers are focusing on targeting epigenetic machinery. The main advantage of targeting epigenetic mechanisms is their reversibility. Thus, cells can be reprogrammed to their normal state. Graph theory is a powerful gift of mathematics which allows us to understand complex networks.

Methodology: In this study, graph theory was utilized for quantitative analysis of the epigenetic network of hepato-cellular carcinoma (HCC) and subsequently finding out the important vertices in the network thus obtained. Secondly, this network was utilized to locate novel targets for hepato-cellular carcinoma epigenetic therapy.

Results: The vertices represent the genes involved in the epigenetic mechanism of HCC. Topological parameters like clustering coefficient, eccentricity, degree, etc. have been evaluated for the assessment of the essentiality of the node in the epigenetic network.

Conclusion: The top ten novel epigenetic target genes involved in HCC reported in this study are cdk6, cdk4, cdkn2a, smad7, smad3, ccnd1, e2f1, sf3b1, ctnnb1, and tgfb1.

PROcket, an Efficient Algorithm to Predict Protein Ligand Binding Site

PROcket, an Efficient Algorithm to Predict Protein Ligand Binding Site

Semwal R., Aier I., Varadwaj P.K., Antsiperov S. (2019) PROcket, an Efficient Algorithm to Predict Protein Ligand Binding Site. In: Rojas I., Valenzuela O., Rojas F., Ortuño F. (eds) Bioinformatics and Biomedical Engineering. IWBBIO 2019. Lecture Notes in Computer Science, vol 11465. Springer, Cham

DOI: https://doi.org/10.1007/978-3-030-17938-0_40

Abstract: To carry out functional annotation of proteins, the most crucial step is to identify the ligand binding site (LBS) information. Although several algorithms have been reported to identify the LBS, most have limited accuracy and efficiency while considering the number and type of geometrical and physio-chemical features used for such predictions. In this proposed work, a fast and accurate algorithm “PROcket” has been implemented and discussed. The algorithm uses grid-based approach to cluster the local residue neighbors that are present on the solvent accessible surface of proteins. Further with inclusion of selected physio-chemical properties and phylogenetically conserved residues, the algorithm enables accurate detection of the LBS. A comparative study with well-known tools; LIGSITE, LIGSITECS, PASS and CASTptool was performed to analyze the performance of our tool. A set of 48 ligand-bound protein structures from different families were used to compare the performance of the tools. The PROcket algorithm outperformed the existing methods in terms of quality and processing speed with 91% accuracy while considering top 3 rank pockets and 98% accuracy considering top 5 rank pockets.