Insights into pathophysiology of dystropy through the analysis of gene networks: an example of bronchial asthma and tuberculosis

Abstract

Co-existence of bronchial asthma (BA) and tuberculosis (TB) is extremely uncommon (dystropic). We assume that this is caused by the interplay between genes involved into specific pathophysiological pathways that arrest simultaneous manifestation of BA and TB. Identification of common and specific genes may be important to determine the molecular genetic mechanisms leading to rare co-occurrence of these diseases and may contribute to the identification of susceptibility genes for each of these dystropic diseases. To address the issue, we propose a new methodological strategy that is based on reconstruction of associative networks that represent molecular relationships between proteins/genes associated with BA and TB, thus facilitating a better understanding of the biological context of antagonistic relationships between the diseases. The results of our study revealed a number of proteins/genes important for the development of both BA and TB.

Network Analysis Identifies SOD2 mRNA as a Potential Biomarker for Parkinson's Disease

“…Although the prioritization method presented in this study has been evaluated in the specific case of PD-T2DM, other disease-disease associations may be studied following this protocol. For instance, the construction of shared genes and protein networks have facilitated the understanding of other disease-disease associations such as asthma and tuberculosis [32] and artherosclerosis-induced ocular diseases [33] . Thus, network analysis of disease comorbidities may reveal novel diagnostic biomarkers and therapeutic strategies.…”

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

“…[63][64][65]. Previously, for such diseases as bronchial asthma and tuberculosis, we showed the potential role of genes concurrently linked with both of them in the pathogenesis of their comorbid relationships [35]. The network of interactions between genes and proteins, associated simultaneously with asthma and hypertension (complete asthma/hypertension network), constructed by intersection of the asthma and hypertension networks, included 85 genes, 201 proteins, and 9638 interactions of 17 types.…”

“…There are a number of resources in the world that allow reconstruction of such associative gene networks, for example, MetaCore [27], Ingenuity [28] and ANDSystem [29,30]. In particular, using the developed by us ANDSystem tool, the following studies were performed: analysis of proteomic data on Helicobacter pylori infection [31]; analysis of the urine proteomic profile in control and under the influence of space flight factors [32]; analysis of tissue-specific gene knockout effect and the search for potential drug targets [33]; analysis of hepatitis C virus life cycle gene networks [34]; analysis of comorbid relations of bronchial asthma and tuberculosis [35], preeclampsia, diabetes and obesity [36], glaucoma [37]; search for novel candidate genes of susceptibility to tuberculosis [38].…”

Molecular Genetic Studies of Comorbidity

“… ðåçóëüòàòå àíàëèçà îáùèõ è ñïåöèôè÷åñêèõ äëÿ êàaeäîãî èç ýòèõ çàáîëåâàíèé áåëêîâ è îöåíêè ìîëåêóëÿðíî-ãåíåòè÷åñêèõ âçàèìîäåéñòâèé ìåaeäó íèìè â ñðàâíåíèè ñî ñëó÷àéíî âûáðàííûìè ïàðàìè áîëåçíåé ïîêàçàíà òåñíàÿ ñâÿçü ìåaeäó àñòìîé è òóáåðêóëåçîì. Âûñîêàÿ ñâÿçàííîñòü áûëà îáíàðóaeèëè òàêaeå äëÿ îíêîëîãè÷åñêèõ (ðàê ëåãêèõ, êîëîðåêòàëüíûé ðàê, ðàê ïðîñòàòû) è íåéðîäåãåíåðàòèâíûõ (áîëåçíü Àëüöãåéìåðà, áîëåçíü Ïàðêèíñîíà è øèçîôðåíèÿ) ïàð áîëåçíåé, èçâåñòíûõ ñâîèìè äèñòðîïíûìè îòíîøåíèÿìè [47]. Ïîäîáíûì aeå îáðàçîì äëÿ êîìîðáèäíûõ áîëåçíåé íà ïðèìåðå ïðåýêëàìïñèè, îaeèðåíèÿ è ñàõàðíîãî äèàáåòà ïîêàçàíà âûðàaeåííàÿ ñâÿçü ìåaeäó áåëêàìè, êîòîðàÿ íå íàáëþäàëàñü äëÿ ñëó÷àéíî âûáðàííûõ ïàð áîëåçíåé [48].…”