Browsing by Subject "Gene ontologies"

Now showing 1 - 4 of 4
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    Computational analysis of candidate disease genes and variants for salt-sensitive hypertension in indigenous Southern Africans
    (Public Library of Science, 2010) Tiffin, Nicki; Meintjes, Ayton; Ramesar, Rajkumar; Bajic, Vladimir B.; Rayner, Brian
    Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor ( PTH ) and type-1angiotensin II receptor ( AGTR1 ). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension.
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    Information content-based gene ontology functional similarity measures: which one to use for a given biological data type?
    (Public Library of Science, 2014) Mazandu, Gaston K; Mulder, Nicola J
    The current increase in Gene Ontology (GO) annotations of proteins in the existing genome databases and their use in different analyses have fostered the improvement of several biomedical and biological applications. To integrate this functional data into different analyses, several protein functional similarity measures based on GO term information content (IC) have been proposed and evaluated, especially in the context of annotation-based measures. In the case of topology-based measures, each approach was set with a specific functional similarity measure depending on its conception and applications for which it was designed. However, it is not clear whether a specific functional similarity measure associated with a given approach is the most appropriate, given a biological data set or an application, i.e., achieving the best performance compared to other functional similarity measures for the biological application under consideration. We show that, in general, a specific functional similarity measure often used with a given term IC or term semantic similarity approach is not always the best for different biological data and applications. We have conducted a performance evaluation of a number of different functional similarity measures using different types of biological data in order to infer the best functional similarity measure for each different term IC and semantic similarity approach. The comparisons of different protein functional similarity measures should help researchers choose the most appropriate measure for the biological application under consideration.
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    Predicting and analyzing interactions between Mycobacterium tuberculosis and its human host
    (Public Library of Science, 2013) Rapanoel, Holifidy A; Mazandu, Gaston K; Mulder, Nicola J
    The outcome of infection by Mycobacterium tuberculosis (Mtb) depends greatly on how the host responds to the bacteria and how the bacteria manipulates the host, which is facilitated by protein-protein interactions. Thus, to understand this process, there is a need for elucidating protein interactions between human and Mtb, which may enable us to characterize specific molecular mechanisms allowing the bacteria to persist and survive under different environmental conditions. In this work, we used the interologs method based on experimentally verified intra-species and inter-species interactions to predict human-Mtb functional interactions. These interactions were further filtered using known human-Mtb interactions and genes that are differentially expressed during infection, producing 190 interactions. Further analysis of the subcellular location of proteins involved in these human-Mtb interactions confirms feasibility of these interactions. We also conducted functional analysis of human and Mtb proteins involved in these interactions, checking whether these proteins play a role in infection and/or disease, and enriching Mtb proteins in a previously predicted list of drug targets. We found that the biological processes of the human interacting proteins suggested their involvement in apoptosis and production of nitric oxide, whereas those of the Mtb interacting proteins were relevant to the intracellular environment of Mtb in the host. Mapping these proteins onto KEGG pathways highlighted proteins belonging to the tuberculosis pathway and also suggested that Mtb proteins might use the host to acquire nutrients, which is in agreement with the intracellular lifestyle of Mtb. This indicates that these interactions can shed light on the interplay between Mtb and its human host and thus, contribute to the process of designing novel drugs with new biological mechanisms of action.
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    Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions
    (Public Library of Science, 2016) Vendelova, Emilia; De Lima, Jeferson Camargo; Lorenzatto, Karina Rodrigues; Monteiro, Karina Mariante; Mueller, Thomas; Veepaschit, Jyotishman; Grimm, Clemens; Brehm, Klaus; Hrčková, Gabriela; Lutz, Manfred B; Ferreira, Henrique B; Nono, Justin Komguep
    Author Summary: The metacestode larval stages of life-threatening tapeworms grow within the organs of its mammalian hosts, thus causing severe and long-lasting morbidity. Immunosuppression, which mainly depends on factors that are released or leaking from the parasite, plays an important role in both survival and proliferation of the larvae. These parasite-derived molecules are potential targets for developing new anti-parasitic drugs and/or improving the effectiveness of current therapies. Moreover, an optimized use of such factors could help to minimize pathologies resulting from uncontrolled immune responses, like allergies and autoimmune diseases. The authors herein demonstrate that larvae from a parasitic cestode release factors that sufficiently support the suppression of dendritic cells, a set of innate immune cells that recognizes and initiates host immune responses against invading pathogens. Employing modern analytic proteomic tools combined with immunological bioassays, several cestode-derived candidate immunomodulators were identified. This is the first bioassay-guided comprehensive library of candidate immunomodulators from a tissue-dwelling cestode larva. This work validates the unmet value of the Mesocestoides corti system in characterizing the mechanisms of host immunomodulation by metacestodes and reveals the largest database of candidate metacestode-derived immunomodulators until date.