SOS genes are rapidly induced while translesion synthesis polymerase activity is temporally regulated.

The DNA damage inducible SOS response in bacteria serves to increase survival of the species at the cost of mutagenesis. The SOS response first initiates error-free repair followed by error-prone repair. Here, we have employed a multi-omics approach to elucidate the temporal coordination of the SOS response.

FunHoP analysis reveals upregulation of mitochondrial genes in prostate cancer.

Mitochondrial activity in cancer cells has been central to cancer research since Otto Warburg first published his thesis on the topic in 1956. Although Warburg proposed that oxidative phosphorylation in the tricarboxylic acid (TCA) cycle was perturbed in cancer, later research has shown that oxidative phosphorylation is activated in most cancers, including prostate cancer (PCa). However, more detailed knowledge on mitochondrial metabolism and metabolic pathways in cancers is still lacking.

The genes controlling normal function of citrate and spermine secretion are lost in aggressive prostate cancer and prostate model systems.

High secretion of the metabolites citrate and spermine is a unique hallmark for normal prostate epithelial cells, and is reduced in aggressive prostate cancer. However, the identity of the genes controlling this biological process is mostly unknown. In this study, we have created a gene signature of 150 genes connected to citrate and spermine secretion in the prostate.

Prediction of recurrence from metabolites and expression of TOP2A and EZH2 in prostate cancer patients treated with radiotherapy.

Background: The dual upregulation of TOP2A and EZH2 gene expression has been proposed as a biomarker for recurrence in prostate cancer patients to be treated with radical prostatectomy. A low tissue level of the metabolite citrate has additionally been connected to aggressive disease and recurrence in this patient group. However, for radiotherapy prostate cancer patients, few prognostic biomarkers have been suggested.

PRL-3 induces a positive signaling circuit between glycolysis and activation of STAT1/2.

Multiple myeloma (MM) is an incurable hematologic malignancy resulting from the clonal expansion of plasma cells. MM cells are interacting with components of the bone marrow microenvironment such as cytokines to survive and proliferate. Phosphatase of regenerating liver (PRL)-3, a cytokine-induced oncogenic phosphatase, is highly expressed in myeloma patients and is a mediator of metabolic reprogramming of cancer cells.

DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation.

Background: Prostate cancer (PCa) has the highest incidence rates of cancers in men in western countries. Unlike several other types of cancer, PCa has few genetic drivers, which has led researchers to look for additional epigenetic and transcriptomic contributors to PCa development and progression. Especially datasets on DNA methylation, the most commonly studied epigenetic marker, have recently been measured and analysed in several PCa patient cohorts.

DNA methylation data by sequencing: experimental approaches and recommendations for tools and pipelines for data analysis.

Sequencing technologies have changed not only our approaches to classical genetics, but also the field of epigenetics. Specific methods allow scientists to identify novel genome-wide epigenetic patterns of DNA methylation down to single-nucleotide resolution. DNA methylation is the most researched epigenetic mark involved in various processes in the human cell, including gene regulation and development of diseases, such as cancer.

Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized.

Background: The relationship between cholesterol and prostate cancer has been extensively studied for decades, where high levels of cellular cholesterol are generally associated with cancer progression and less favorable outcomes. However, the role of in vivo cellular cholesterol synthesis in this process is unclear, and data on the transcriptional activity of cholesterol synthesis pathway genes in tissue from prostate cancer patients are inconsistent.

Methods: A common problem with cancer tissue data from patient cohorts is the presence of heterogeneous tissue which confounds molecular analysis of the samples.

Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer.

TMPRSS2-ERG has been proposed to be a prognostic marker for prostate cancer. The aim of this study was to identify changes in metabolism, genes and biochemical recurrence related to TMPRSS2-ERG by using an integrated approach, combining metabolomics, transcriptomics, histopathology and clinical data in a cohort of 129 human prostate samples (41 patients). Metabolic analyses revealed lower concentrations of citrate and spermine comparing ERGhigh to ERGlow samples, suggesting an increased cancer aggressiveness of ERGhigh compared to ERGlow.

A Balanced Tissue Composition Reveals New Metabolic and Gene Expression Markers in Prostate Cancer.

Molecular analysis of patient tissue samples is essential to characterize the in vivo variability in human cancers which are not accessible in cell-lines or animal models. This applies particularly to studies of tumor metabolism. The challenge is, however, the complex mixture of various tissue types within each sample, such as benign epithelium, stroma and cancer tissue, which can introduce systematic biases when cancers are compared to normal samples.

Phosphatase of regenerating liver 3 (PRL-3) is overexpressed in human prostate cancer tissue and promotes growth and migration.

Background: PRL-3 is a phosphatase implicated in oncogenesis in multiple cancers. In some cancers, notably carcinomas, PRL-3 is also associated with inferior prognosis and increased metastatic potential. In this study we investigated the expression of PRL-3 mRNA in fresh-frozen samples from patients undergoing radical prostatectomy because of prostate cancer (PC) and the biological function of PRL-3 in prostate cancer cells.

Gene signatures ESC, MYC and ERG-fusion are early markers of a potentially dangerous subtype of prostate cancer.

Background: Good prognostic tools for predicting disease progression in early stage prostate cancer (PCa) are still missing. Detection of molecular subtypes, for instance by using microarray gene technology, can give new prognostic information which can assist personalized treatment planning. The detection of new subtypes with validation across additional and larger patient cohorts is important for bringing a potential prognostic tool into the clinic.

A ChIP-Seq benchmark shows that sequence conservation mainly improves detection of strong transcription factor binding sites.

Background: Transcription factors are important controllers of gene expression and mapping transcription factor binding sites (TFBS) is key to inferring transcription factor regulatory networks. Several methods for predicting TFBS exist, but there are no standard genome-wide datasets on which to assess the performance of these prediction methods. Also, it is believed that information about sequence conservation across different genomes can generally improve accuracy of motif-based predictors, but it is not clear under what circumstances use of conservation is most beneficial.

A manually curated ChIP-seq benchmark demonstrates room for improvement in current peak-finder programs.

Chromatin immunoprecipitation (ChIP) followed by high throughput sequencing (ChIP-seq) is rapidly becoming the method of choice for discovering cell-specific transcription factor binding locations genome wide. By aligning sequenced tags to the genome, binding locations appear as peaks in the tag profile. Several programs have been designed to identify such peaks, but program evaluation has been difficult due to the lack of benchmark data sets.

An improved pixel-based approach for analyzing images in two-dimensional gel electrophoresis.

An improved pixel-based approach for analyzing 2-DE images is presented. The key feature of the method is to create a mask based on all gels in the experiment using image morphology, followed by multivariate analysis on the pixel level. The method reduces the impact of noise and background by identifying regions in the image where protein spots are present, but make no assumption on individual spot boundaries for isolated spots.

A multivariate spot filtering model for two-dimensional gel electrophoresis.

Image segmentation plays an important role in the automatic analysis of protein spots in 2-DE. Using image segments representing protein spots, the amount of protein in each segment can be quantified, and corresponding segments can be matched and compared for multiple gels. However, the common presence of image segments caused by noise and unwanted artefacts highly disturb the analysis and comparison of the gels.

A new method for assigning common spot boundaries for multiple gels in two-dimensional gel electrophoresis.

The benefits of defining common spot boundaries when several gels from 2-DE are compared and analyzed have lately been stressed by both commercial software producers and users of this software. Though the importance of common spot boundaries is clearly stated, few reports exist that target this issue explicitly. In this study a method for defining common spots boundaries is developed, called the spot density method.