Multi-Factored Gene-Gene Proximity Measures Exploiting Biological Knowledge Extracted from Gene Ontology: Application in Gene Clustering.

To describe the cellular functions of proteins and genes, a potential dynamic vocabulary is Gene Ontology (GO), which comprises of three sub-ontologies namely, Biological-process, Cellular-component, and Molecular-function. It has several applications in the field of bioinformatics like annotating/measuring gene-gene or protein-protein semantic similarity, identifying genes/proteins by their GO annotations for disease gene and target discovery, etc. To determine semantic similarity between genes, several semantic measures have been proposed in literature, which involve information content of GO-terms, GO tree structure, or the combination of both. But, most of the existing semantic similarity measures do not consider different topological and information theoretic aspects of GO-terms collectively. Inspired by this fact, in this article, we have first proposed three novel semantic similarity/distance measures for genes covering different aspects of GO-tree. These are further implanted in the frameworks of well-known multi-objective and single-objective based clustering algorithms to determine functionally similar genes. For comparative analysis, 10 popular existing GO based semantic similarity/distance measures and tools are also considered. Experimental results on Mouse genome, Yeast, and Human genome datasets evidently demonstrate the supremacy of multi-objective clustering algorithms in association with proposed multi-factored similarity/distance measures. Clustering outcomes are further validated by conducting some biological/statistical significance tests. Supplementary information is available at https://www.iitp.ac.in/sriparna/journals.html.

Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering.

In recent years DNA microarray technology, leading to the generation of high-volume biological data, has gained significant attention. To analyze this high volume gene-expression data, one such powerful tool is Clustering. For any clustering algorithm, its efficiency majorly depends upon the underlying similarity/dissimilarity measure. During the analysis of such data often there is a need to further explore the similarity of genes not only with respect to their expression values but also with respect to their functional annotations, which can be obtained from Gene Ontology (GO) databases. In the existing literature, several novel clustering and bi-clustering approaches were proposed to identify co-regulated genes from gene-expression datasets. Identifying co-regulated genes from gene expression data misses some important biological information about functionalities of genes, which is necessary to identify semantically related genes. In this paper, we have proposed sixteen different semantic gene-gene dissimilarity measures utilizing biological information of genes retrieved from a global biological database namely Gene Ontology (GO). Four proximity measures, viz. Euclidean, Cosine, point symmetry and line symmetry are utilized along with four different representations of gene-GO-term annotation vectors to develop total sixteen gene-gene dissimilarity measures. In order to illustrate the profitability of developed dissimilarity measures, some multi-objective as well as single-objective clustering algorithms are applied utilizing proposed measures to identify functionally similar genes from Mouse genome and Yeast datasets. Furthermore, we have compared the performance of our proposed sixteen dissimilarity measures with three existing state-of-the-art semantic similarity and distance measures.

Malarial anaemia and nitric oxide induced megaloblastic anaemia: a review on the causes of malarial anaemia.

Direct destruction and ineffective erythropoesis does not adequately explain the cause of anaemia in malaria. It is possible that there are more other mechanisms involved besides the causes described till date in malarial anaemia. The effect of NO on erythropoesis and a major haematological abnormality (microcytic/normocytic/megaloblastic picture) can significantly be observed on repeated exposure. In addition, NO can inhibit the enzyme methionine synthase so functional vit B12 deficiency state may occur which can lead to megaloblastic anaemia. This review will focus on causation of malarial anaemia and nitric oxide induced megaloblastic anaemia.