A functional variant on 20q13.33 related to glioma risk alters enhancer activity and modulates expression of multiple genes.

Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with glioma risk on 20q13.33, but the biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 20q13.33 impacted the activity of an enhancer, leading to an altered expression of nearby genes. To identify candidate functional SNPs, we identified all SNPs in linkage disequilibrium with the risk-associated SNP rs2297440 that mapped to putative enhancers. Putative enhancers containing candidate functional SNPs were tested for allele-specific effects in luciferase enhancer activity assays against glioblastoma multiforme (GBM) cell lines. An enhancer containing SNP rs3761124 exhibited allele-specific effects on activity. Deletion of this enhancer by CRISPR-Cas9 editing in GBM cell lines correlated with an altered expression of multiple genes, including STMN3, RTEL1, RTEL1-TNFRSF6B, GMEB2, and SRMS. Expression quantitative trait loci (eQTL) analyses using nondiseased brain samples, isocitrate dehydrogenase 1 (IDH1) wild-type glioma, and neurodevelopmental tissues showed STMN3 to be a consistent significant eQTL with rs3761124. RTEL1 and GMEB2 were also significant eQTLs in the context of early CNS development and/or in IDH1 wild-type glioma. We provide evidence that rs3761124 is a functional variant on 20q13.33 related to glioma/GBM risk that modulates the expression of STMN3 and potentially other genes across diverse cellular contexts

List of all fields defined for STATdb records.

<p>Fields that provide information selected from the source record (NCBI Entrez Protein database) are marked as “Source”. “Assigned” fields are those not found in the source record, but were included to provide information obtained from analysis of the sequence data, existing annotations or the literature.</p>#<p><i>NCBI Entrez protein database.</i></p>$<p><i>The respective literature are indicated in the relevant records.</i></p><p>List of all fields defined for STATdb records.</p

Performance measures of STATdbPredict (RPS-BLAST and BLASTp) versus standalone BLASTp search.

<p>Performance measures of STATdbPredict (RPS-BLAST and BLASTp) versus standalone BLASTp search.</p

STATdbPredict output report page for STAT_00001.

<p>The alignment is cropped to save space.</p

Exploring the role of cerebrospinal fluid as analyte in neurologic disorders.

The cerebrospinal fluid (CSF) is a clear ultrafiltrate of blood that envelopes and protects the central nervous system while regulating neuronal function through the maintenance of interstitial fluid homeostasis in the brain. Due to its anatomic location and physiological functions, the CSF can provide a reliable source of biomarkers for the diagnosis and treatment monitoring of different neurological diseases, including neurodegenerative diseases such as Alzheimer\u27s disease, Parkinson\u27s disease, amyotrophic lateral sclerosis, and primary and secondary brain malignancies. The incorporation of CSF biomarkers into the drug discovery and development can improve the efficiency of drug development and increase the chances of success. This review aims to consolidate the current use of CSF biomarkers in clinical practice and explore future perspectives for the field

MTAP loss: a possible therapeutic approach for glioblastoma

Abstract Glioblastoma is the most lethal form of brain tumor with a recurrence rate of almost 90% and a survival time of only 15 months post-diagnosis. It is a highly heterogeneous, aggressive, and extensively studied tumor. Multiple studies have proposed therapeutic approaches to mitigate or improve the survival for patients with glioblastoma. In this article, we review the loss of the 5′-methylthioadenosine phosphorylase (MTAP) gene as a potential therapeutic approach for treating glioblastoma. MTAP encodes a metabolic enzyme required for the metabolism of polyamines and purines leading to DNA synthesis. Multiple studies have explored the loss of this gene and have shown its relevance as a therapeutic approach to glioblastoma tumor mitigation; however, other studies show that the loss of MTAP does not have a major impact on the course of the disease. This article reviews the contrasting findings of MTAP loss with regard to mitigating the effects of glioblastoma, and also focuses on multiple aspects of MTAP loss in glioblastoma by providing insights into the known findings and some of the unexplored areas of this field where new approaches can be imagined for novel glioblastoma therapeutics

Anomaly Detection Framework for Wearables Data: A Perspective Review on Data Concepts, Data Analysis Algorithms and Prospects

Wearable devices use sensors to evaluate physiological parameters, such as the heart rate, pulse rate, number of steps taken, body fat and diet. The continuous monitoring of physiological parameters offers a potential solution to assess personal healthcare. Identifying outliers or anomalies in heart rates and other features can help identify patterns that can play a significant role in understanding the underlying cause of disease states. Since anomalies are present within the vast amount of data generated by wearable device sensors, identifying anomalies requires accurate automated techniques. Given the clinical significance of anomalies and their impact on diagnosis and treatment, a wide range of detection methods have been proposed to detect anomalies. Much of what is reported herein is based on previously published literature. Clinical studies employing wearable devices are also increasing. In this article, we review the nature of the wearables-associated data and the downstream processing methods for detecting anomalies. In addition, we also review supervised and un-supervised techniques as well as semi-supervised methods that overcome the challenges of missing and un-annotated healthcare data