Machine learning based predictive model and systems-level network of host-microbe interactions in post-COVID-19 mucormycosis.

Mucormycosis, a rare infection is caused by fungi Mucorales. The affiliation of mucormycosis with Coronavirus disease (COVID-19) is a rising issue of concern in India. There have been numerous case reports of association of rhino-cerebral-orbital, angioinvasive, pulmonary, respiratory and gastrointestinal tract related mucormycosis in patients with history of COVID-19. The immune dysregulation, preposterous use of steroids, interleukin-6-directed therapies and mechanical ventilation in COVID-19 immunocompromised individuals hypothesizes and predisposes to advancement of mucormycosis. The gaps in mode of presentation, disease course, diagnosis and treatment of post-COVID-19 mucormycosis requires critical analysis in order to control its morbidity and incidence and for prevention and management of opportunistic infections in COVID-19 patients. Our study performs machine learning, systems biology and bioinformatics analysis of post-COVID-19 mucormycosis in India incorporating multitudinous techniques. Text mining identifies candidate characteristics of post-COVID-19 mucormycosis cases including city, gender, age, symptoms, clinical parameters, microorganisms and treatment. The characteristics are incorporated in a machine learning based disease model resulting in predictive potentiality of characteristics of post-COVID-19 mucormycosis. The characteristics are used to create a host-microbe interaction disease network comprising of interactions between microorganism, host-microbe proteins, non-specific markers, symptoms and drugs resulting in candidate molecules. R1A (Replicase polyprotein 1a) and RPS6 (Ribosomal Protein S6) are yielded as potential drug target and biomarker respectively via potentiality analysis and expression in patients. The potential risk factors, drug target and biomarker can serve as prognostic, early diagnostic and therapeutic molecules in post-COVID-19 mucormycosis requiring further experimental validation and analysis on post-COVID-19 mucormycosis cases.

Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach.

Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe 'interspecies communication', using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA.Our study identified Na(+)/H(+) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.

Association of Inflammatory Bowel Disease with Arthritis: Evidence from In Silico Gene Expression Patterns and Network Topological Analysis.

Inflammatory bowel disease (IBD) is an idiopathic prolonged ailment accountable for inflammatory conditions of the intestine. Moreover, arthritis is responsible for joints' stiffness and painful inflammation. IBD shows certain articular extra-intestinal manifestations associating IBD with arthritis. IBD associated arthritis is found to be linked with ankylosing spondylitis (AS). The present study insights for the potential and putative drug targets and biomarkers of IBD associated with arthritis using in silico approaches. Microarray data analysis of datasets involving IBD affected and AS affected vs controls were done to explore the differentially expressed genes (DEGs). In majority of the datasets, the common DEGs found were sterile alpha motif domain containing 9 like (SAMD9L), inhibin beta A subunit (INHBA), transmembrane protein 45A (TMEM45A) and transmembrane and tetratricopeptide repeat containing 1 (TMTC1). The common functions and pathways found between the DEGs were control of macromolecule metabolism process, control of metabolic process, control of primary metabolic process, and control of protein metabolic process, cell differentiation, organ development, single-organism development process, multicellular organism development process, development of system, single-multicellular organism development process, developmental process, development of anatomical structure, multicellular organismal development process, control of biological process, cell proliferation, hematopoietic progenitor cell differentiation and immune system process. TMTC1 and INBHA were found to be more biologically significant genes according to the topological properties of the network. This study also suggests that TMTC1, INBHA, TMEM45A and SAMD9L DEGs and their accompanying pathways might have the potential to be exploited as drug targets and biomarkers in the diagnosis and/or treatment of IBD linked arthritis and warrants for further experimental validation.

Computational based functional analysis of Bacillus phytases.

Phytase is an enzyme which catalyzes the total hydrolysis of phytate to less phosphorylated myo-inositol derivatives and inorganic phosphate and digests the undigestable phytate part present in seeds and grains and therefore provides digestible phosphorus, calcium and other mineral nutrients. Phytases are frequently added to the feed of monogastric animals so that bioavailability of phytic acid-bound phosphate increases, ultimately enhancing the nutritional value of diets. The Bacillus phytase is very suitable to be used in animal feed because of its optimum pH with excellent thermal stability. Present study is aimed to perform an in silico comparative characterization and functional analysis of phytases from Bacillus amyloliquefaciens to explore physico-chemical properties using various bio-computational tools. All proteins are acidic and thermostable and can be used as suitable candidates in the feed industry.

An in-silico insight into the characteristics of ß-propeller phytase.

Phytase is an enzyme that is found extensively in the plant kingdom and in some species of bacteria and fungi. This paper identifies and analyses the available full length sequences of ß-propeller phytases (BPP). BPP was chosen due to its potential applicability in the field of aquaculture. The sequences were obtained from the Uniprot database and subject to various online bioinformatics tools to elucidate the physio-chemical characteristics, secondary structures and active site compositions of BPP. Protparam and SOPMA were used to analyse the physiochemical and secondary structure characteristics, while the Expasy online modelling tool and CASTp were used to model the 3-D structure and identify the active sites of the BPP sequences. The amino acid compositions of the four sequences were compared and composed in a graphical format to identify similarities and highlight the potentially important amino acids that form the active site of BPP. This study aims to analyse BPP and contribute to the clarification of the molecular mechanism involved in the enzyme activity of BPP and contribute in part to the possibility of constructing a synthetic version of BPP.

The Wnt pathway: emerging anticancer strategies.

The canonical Wnt cascade has emerged as a critical regulator of cancer cells. Activation of the Wnt signaling pathway has also been associated with stem cell, thus raising the possibility of its role in embryogenesis and in the proliferation of malignant cancer cells. Wnt pathway has been reported to be involved in normal physiological processes in adult animals and integrally associated with cancer cell growth and maintenance, thus has been harnessed to devise strategies for anticancer therapy. The presence or absence of some members in this pathway, such as ß-catenin, Axin or APC, has been found to involve in different types of tumors in human beings. Dysregulation of the canonical Wnt/ß-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of ß-catenin, has been implicated in colorectal tumorigenesis. Further, elevated levels of ß-catenin protein, a hallmark of activated canonical Wnt pathway, have been significantly observed in common forms of human malignancies, indicating that activation of the Wnt pathway may play an important role in tumor development and hence could be a crucial consideration for drug development. The paper discusses the potential therapeutic and diagnostic strategies directing on Wnt pathways on the basis of recent patents and their analysis.