The evolutionarily conserved p53 protein and its cellular pathways mediate tumour suppression through an informed, regulated and integrated set of responses to environmental perturbations resulting ...in either cellular death or the maintenance of cellular homeostasis. The p53 and MDM2 proteins form a central hub in this pathway that receives stressful inputs via MDM2 and respond via p53 by informing and altering a great many other pathways and functions in the cell. The MDM2-p53 hub is one of the hubs most highly connected to other signalling pathways in the cell, and this may be why TP53 is the most commonly mutated gene in human cancers. Initial or truncal TP53 gene mutations (the first mutations in a stem cell) are selected for early in cancer development inectodermal and mesodermal-derived tissue-specific stem and progenitor cells and then, following additional mutations, produce tumours from those tissue types. In endodermal-derived tissue-specific stem or progenitor cells, TP53 mutations are functionally selected as late mutations transitioning the mutated cell into a malignant tumour. The order in which oncogenes or tumour suppressor genes are functionally selected for in a stem cell impacts the timing and development of a tumour.
Abstract
Gene co-expression networks can be used to associate genes of unknown function with biological processes, to prioritize candidate disease genes or to discern transcriptional regulatory ...programmes. With recent advances in transcriptomics and next-generation sequencing, co-expression networks constructed from RNA sequencing data also enable the inference of functions and disease associations for non-coding genes and splice variants. Although gene co-expression networks typically do not provide information about causality, emerging methods for differential co-expression analysis are enabling the identification of regulatory genes underlying various phenotypes. Here, we introduce and guide researchers through a (differential) co-expression analysis. We provide an overview of methods and tools used to create and analyse co-expression networks constructed from gene expression data, and we explain how these can be used to identify genes with a regulatory role in disease. Furthermore, we discuss the integration of other data types with co-expression networks and offer future perspectives of co-expression analysis.
SUMMARY
Soybean (Glycine max L. Merr.) is a major crop in animal feed and human nutrition, mainly for its rich protein and oil contents. The remarkable rise in soybean transcriptome studies over the ...past 5 years generated an enormous amount of RNA‐seq data, encompassing various tissues, developmental conditions and genotypes. In this study, we have collected data from 1298 publicly available soybean transcriptome samples, processed the raw sequencing reads and mapped them to the soybean reference genome in a systematic fashion. We found that 94% of the annotated genes (52 737/56 044) had detectable expression in at least one sample. Unsupervised clustering revealed three major groups, comprising samples from aerial, underground and seed/seed‐related parts. We found 452 genes with uniform and constant expression levels, supporting their roles as housekeeping genes. On the other hand, 1349 genes showed heavily biased expression patterns towards particular tissues. A transcript‐level analysis revealed that 95% (70 963 of 74 490) of the assembled transcripts have intron chains exactly matching those from known transcripts, whereas 3256 assembled transcripts represent potentially novel splicing isoforms. The dataset compiled here constitute a new resource for the community, which can be downloaded or accessed through a user‐friendly web interface at http://venanciogroup.uenf.br/resources/. This comprehensive transcriptome atlas will likely accelerate research on soybean genetics and genomics.
Significance Statement
Here we report an integrative and systematic analysis of 1298 RNA‐Seq samples to build a soybean gene expression atlas. This resource is accessible via a user‐friendly web interface as well as available for download.
Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of ...patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio OR = 2.666 1.471–4.882; p = 0.0013) but not FTD (odds ratio OR = 1.446 0.558–3.574; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio HR 1.74 1.18, 2.56, p = 0.005), more frequent limb onset (odds ratio OR = 2.34 1.093–4.936; p = 0.028) and a family history of ALS (odds ratio OR = 2.538 1.375–4.634; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.
Summary
Arabidopsis thaliana is a long established model species for plant molecular biology, genetics and genomics, and studies of A. thaliana gene function provide the basis for formulating ...hypotheses and designing experiments involving other plants, including economically important species. A comprehensive understanding of the A. thaliana genome and a detailed and accurate understanding of the expression of its associated genes is therefore of great importance for both fundamental research and practical applications. Such goal is reliant on the development of new genetic and genomic resources, involving new methods of data acquisition and analysis. We present here the genome‐wide analysis of A. thaliana gene expression profiles across different organs and developmental stages using high‐throughput transcriptome sequencing. The expression of 25 706 protein‐coding genes, as well as their stability and their spatiotemporal specificity, was assessed in 79 organs and developmental stages. A search for alternative splicing events identified 37 873 previously unreported splice junctions, approximately 30% of them occurred in intergenic regions. These potentially represent novel spliced genes that are not included in the TAIR10 database. These data are housed in an open‐access web‐based database, TraVA (Transcriptome Variation Analysis, http://travadb.org/), which allows visualization and analysis of gene expression profiles and differential gene expression between organs and developmental stages.
Significance Statement
The development and update of genetic and genomic resources, involving new methods of data acquisition and analysis, is necessary even for such long established model organisms such as Arabidopsis thaliana. We present a transcriptome map of A. thaliana created using high‐throughput RNA sequencing. It covers 79 organs and developmental stages; the analysis allowed the determination of global characteristics of the A. thaliana transcriptome and to add splice junctions and predicted genes to our current knowledge of the A. thaliana genome.
Cancer treatment has been always considered one of the most critical and vital themes of clinical issues. Many approaches have been developed, depending on the type and the stage of tumor. Gene ...therapy has the potential to revolutionize different cancer therapy. With the advent of recent bioinformatics technologies and genetic science, it become possible to identify, diagnose and determine the potential treatment using the technology of gene delivery. Several approaches have been developed and experimented in vitro and vivo for cancer therapy including: naked nucleic acids based therapy, targeting micro RNAs, oncolytic virotherapy, suicide gene based therapy, targeting telomerase, cell mediated gene therapy, and CRISPR/Cas9 based therapy. In this review, we present a straightforward introduction to cancer biology and occurrence, highlighting different viral and non-viral gene delivery systems for gene therapy and critically discussed the current and various strategies for cancer gene therapy.
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