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Pal, J. K.

Publications and source records attributed to Pal, J. K..

2 recordsLinked to original sources

Machine learning based identification of candidate miRNA biomarkers for micro-invasive breast cancer diagnosis

Abstract PurposeEarly detection of cancer can be done by analyzing miRNA expression patterns. miRNAs play a significant role in biological processes, and they have been identified as one of the major biomarkers in cancer. miRNAs can also be detected in human blood (micro-invasive way of sample collection), which makes the diagnostic procedure much less stressful for the patients. In this article, we emphasize on identification of miRNAs as biomarkers (collected from blood sample) that are associated with breast cancer. MethodsIn this investigation we use three breast cancer data sets, obtained from blood samples. A combination of multiple feature selection and classification models is used to classify normal vs cancer samples. In the first stage, the significant miRNAs associated with cancer were selected by (a) classifier assigned weights and (b) feature selection algorithms. In the second stage, we apply multiple classifiers to observe the diagnostic capability of the selected miRNAs for consideration as potential biomarkers. ResultsOur miRNA selection stage identified ten miRNAs, which were subsequently analysed using multiple classifiers for their ability to distinguish between normal and cancerous cases. The performance is examined using a 5-fold cross validation technique using multiple measures such as precision, recall, F1-score, and accuracy. We also use a confusion matrix to evaluate the performance of the selected miRNAs. For two out of three datasets, we achieve satisfactory performance in terms of normal vs cancer classification. ConclusionWe observe that high expression levels of miRNA is relatively more important than the sample size, for effective blood-based diagnosis of breast cancer. The novelty of our investigation lies in combining three aspects viz., blood-based breast cancer diagnosis, use of multiple ML based feature selection algorithms to identify the miRNAs associated with breast cancer, evaluating them using various classifiers and the robustness of these ML models in feature selection and classification.

cancer biology↗

An intracellular tripeptide Arg-His-Trp of serum origin detected in MCF-7 cells is a possible agonist to β2 adrenoceptor

BackgroundThe need of agonists and antagonists of {beta}2 adrenoceptor ({beta}2AR) is warranted in various human disease conditions including cancer, cardiovascular and other metabolic disorders. However, the sources of agonists of {beta}2AR are diverse in nature. Interestingly, there is a complete gap in the exploration of agonists of {beta}2AR from serum that is a well-known component of culture media which supports growth and proliferation of normal and cancer cells in vitro. MethodsIn this paper, we employed a novel vertical tube gel electrophoresis (VTGE)-assisted purification of intracellular metabolites of MCF-7 cells grown in vitro in complete media with fetal bovine serum (FBS). Intracellular metabolites of MCF-7 cells were then analyzed by LC-HRMS. Identified intracellular tripeptides of FBS origin were evaluated for their molecular interactions with various extracellular and intracellular receptors including {beta}2AR (PDB ID: 2RH1) by employing molecular docking and molecular dynamics simulations (MDS). A known agonist of {beta}2AR, isoproterenol was used as a positive control in molecular docking and MDS analyses ResultsWe report here identification of a few novel intracellular tripeptides, namely Arg-His-Trp, (PubChem CID-145453842), Pro-Ile-Glu, (PubChem CID-145457492), Cys-Gln-Gln, (PubChem CID-71471965), Glu-Glu-Lys, (PubChem CID-11441068) and Gly-Cys-Leu (PubChem CID145455600) of FBS origin in MCF-7 cells. Molecular docking and MDS analyses revealed that among these molecules, the tripeptide Arg-His-Trp shows a favorable binding affinity with {beta}2AR (-9.8 Kcal/mol). Furthermore, agonistic effect of this tripeptide, Arg-His-Trp is significant and comparable with that of a known agonist of {beta}2AR, isoproterenol. ConclusionIn conclusion, we identified a unique Arg-His-Trp tripeptide of FBS origin in MCF-7 cells by employing a novel approach. This unique tripeptide Arg-His-Trp is suggested to be a potential agonist of {beta}2AR and it may have applications in the context of various human diseases like bronchial asthma and chronic obstructive pulmonary disease (COPD). NOVELTY & IMPACT STATEMENTSO_LIThis paper reports on a novel vertical tube gel electrophoresis (VTGE) system that assisted in the purification and identification of a few intracellular tripeptides in the in vitro grown breast cancer cells, MCF-7ls. C_LIO_LIMolecular docking and molecular dynamics simulation analyses strongly suggest that the tripeptide Arg-His-Trp among others forms the most stable ligand-protein complex with {beta}2 adrenoceptor ({beta}2AR). Its binding affinity and the nature of molecular interactions are comparable or even better than the known agonists of {beta}2AR. C_LIO_LIThis tripeptide Arg-His-Trp is predicted to show manyfold less cytotoxicity, mutagenicity, cardiotoxicity, drug-drug interactions, microsomal stability, and drug-induced liver injury over the other known agonists of {beta}2AR. C_LIO_LIThe tripeptide Arg-His-Trp is therefore suggested as an effective agonist of {beta}2AR and this may be validated in future, in preclinical and clinical models. C_LI

cell biology↗