Yilmaz, A. | Search bioRxiv

bioRxiv2020

Network based multifactorial modelling of miRNA-target interactions

Competing endogenous RNA (ceRNA) regulations and crosstalk between various types of non-coding RNA in human is an important and under-explored subject. Several studies have pointed out that an alteration in miRNA:target interaction can result in unexpected changes due to indirect and complex interactions. In this paper, we defined a new network-based model that incorporates miRNA:ceRNA interactions with expression values and then calculates network-wide effects after perturbation in expression level of element(s) while utilizing miRNA interaction factors such as seed type, binding energy. We have carried out analysis of large scale miRNA:target networks from breast cancer patients. Highly perturbing genes identified by our approach coincide with breast cancer associated genes and miRNAs. Our network-based approach helps unveiling the crosstalk between node elements in miRNA:target network where abundance of targets leading to sponge effect is taken into account. The model has potential to reveal unforeseen and unpredicted regulations which are only evident when considered in network context. Our tool is scalable and can be plugged in with emerging miRNA effectors such as circRNAs, lncRNAs and available as R package ceRNAnet-sim https://www.bioconductor.org/packages/release/bioc/html/ceRNAnetsim.html.

bioinformatics↗

bioRxiv2020

Gut microbiome dysbiosis is associated with elevated toxic bile acids in Parkinson's disease

The gut microbiome can impact brain health and is altered in Parkinsons disease (PD) patients. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. We find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Proteomic and transcript analysis corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis reveals an increase in microbially-derived, toxic secondary bile acids. Synucleinopathy in mice induces similar microbiome alterations to those of PD patients. The mouse model of synucleinopathy has elevated DCA and LCA. An analysis of blood markers shows evidence of biliary abnormalities early in PD, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.

neuroscience↗