Heidari, E. | Search bioRxiv

bioRxiv2018

A Novel Workflow for Helth Survey Analysis: Results on the Yazd Health Study (YaHS)

Health surveys are one of the most prominent sources of information in medical sciences. Analysis of a health survey not only gives information about the inherent features of the population under study but also sheds light on the interactions between different health factors. Even though there has been a multitude of methodologies proposed for survey analysis, many of them are biased towards the previous hypotheses, the fact which may lead to spurious results by neglecting the whole structure of relations among the factors. Here, we proposed our novel workflow on survey analysis. By gathering the previously less-utilized graphical models on survey analysis, newly-proposed methods, and commonly-used tools of prediction and hypothesis testing our workflow provides the medical community with an end-to-end pipeline for comprehensive statistical analysis of health surveys. To demonstrate the functionality of our workflow, we validate it on the Yazd Health Study (YaHS) dataset, in which a questionnaire of 300 questions from 10000 participants associated with 40 laboratory measurements from a subset of 4010 individuals is acquired from the residents of the Yazd greater area of Iran. Many of our findings are aligned with previous medical knowledge. Most of our novel findings are surprisingly observed in the clinics, each of which is potential to raise a promising hypothesis.

bioinformatics↗

bioRxiv2018

Pin1 Regulatory miRNAs as Novel Candidates for Alzheimer’s Disease Treatment

Alzheimers disease (AD) is the sixth leading cause of death in elderly people whose pathological hallmarks include senile plaques and neurofibrillary tangles (NFTs). The tangles are composed of hyperphosphorylated tau, which is a microtubule-associated protein and its hyperphosphorylation would result in its aggregation and neural cell death. Recently, it has been shown that phosphorylated tau at Thr231 exists in two distinct cis & trans conformations, whose conversion is being mediated by Pin1 isomerase and that the cis, but not the trans, is extremely neurotoxic and drives tau hyperphosphorylation. It has been demonstrated that Pin1 inhibition reflects cis pT231-tau accumulation in neurons but its overactivation is observed in cancer stem cells. Hence, a precise Pin1 regulation is required to keep cells in healthy conditions. As miRNAs play a crucial role in fine-tuning of the gene-expression level, we hypothesized that they might regulate the Pin1 dosage. Nonetheless, the possible regulatory roles of miRNAs in progression of AD by regulating PIN1 is not well studied. We aimed to identify potential miRNAs that down-regulate PIN1 in AD. This can uncover new regulatory mechanisms that result in AD. Thus, we performed a comprehensive study of miRNAs, capable in regulating Pin1, through whole-genome meta-analysis by integrating miRNA expression profiles of 846 different biological samples, along with a systematic literature review and data mining of multiple experimental and predicted miRNA-target databases. We created a list of 56 candidates, which was then short-listed to 10 miRNAs with vigorous experimental evidence. We examined the expression patterns of these miRNAs in the AD and healthy controls and integrated mRNA and miRNA expression profiles to study possible interactions between miRNAs and Pin1. Moreover, we performed an in-silico functional analysis by integrating data of knock-in and knock-down experiments of the candidate miRNAs, and highlighted miR296-5p, miR200b, miR200c, miR140-5p, and miR874 as strong candidate Pin1 regulators. These findings would have profound implications in developing novel therapeutic strategies for AD by blocking expression of highlighted miRNAs using antagomirs.

neuroscience↗