Profiling the epigenome using long-read sequencing.

The advent of single-molecule, long-read sequencing (LRS) technologies by Oxford Nanopore Technologies and Pacific Biosciences has revolutionized genomics, transcriptomics and, more recently, epigenomics research. These technologies offer distinct advantages, including the direct detection of methylated DNA and simultaneous assessment of DNA sequences spanning multiple kilobases along with their modifications at the single-molecule level. This has enabled the development of new assays for analyzing chromatin states and made it possible to integrate data for DNA methylation, chromatin accessibility, transcription factor binding and histone modifications, thereby facilitating comprehensive epigenomic profiling.

Evaluation of strategies for evidence-driven genome annotation using long-read RNA-seq.

While the production of a draft genome has become more accessible due to long-read sequencing, the annotation of these new genomes has not been developed at the same pace. Long-read RNA sequencing (lrRNA-seq) offers a promising solution for enhancing gene annotation. In this study, we explore how sequencing platforms, Oxford Nanopore R9.

Steering research on mRNA splicing in cancer towards clinical translation.

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers.

SQANTI-reads: a tool for the quality assessment of long read data in multi-sample lrRNA-seq experiments.

SQANTI-reads leverages SQANTI3, a tool for the analysis of the quality of transcript models, to develop a read-level quality control framework for replicated long-read RNA-seq experiments. The number and distribution of reads, as well as the number and distribution of unique junction chains (transcript splicing patterns), in SQANTI3 structural categories are informative of raw data quality. Multi-sample visualizations of QC metrics are presented by experimental design factors to identify outliers.

scMaSigPro: Differential Expression Analysis along Single-Cell Trajectories.

Motivation: Understanding the dynamics of gene expression across different cellular states is crucial for discerning the mechanisms underneath cellular differentiation. Genes that exhibit variation in mean expression as a function of Pseudotime and between branching trajectories are expected to govern cell fate decisions. We introduce scMaSigPro, a method for the identification of differential gene expression patterns along Pseudotime and branching paths simultaneously.

SQANTI3: curation of long-read transcriptomes for accurate identification of known and novel isoforms.

SQANTI3 is a tool designed for the quality control, curation and annotation of long-read transcript models obtained with third-generation sequencing technologies. Leveraging its annotation framework, SQANTI3 calculates quality descriptors of transcript models, junctions and transcript ends. With this information, potential artifacts can be identified and replaced with reliable sequences.

Nucleotide-level distance metrics to quantify alternative splicing implemented in TranD.

Advances in affordable transcriptome sequencing combined with better exon and gene prediction has motivated many to compare transcription across the tree of life. We develop a mathematical framework to calculate complexity and compare transcript models. Structural features, i.

SQANTI-SIM: a simulator of controlled transcript novelty for lrRNA-seq benchmark.

Long-read RNA sequencing has emerged as a powerful tool for transcript discovery, even in well-annotated organisms. However, assessing the accuracy of different methods in identifying annotated and novel transcripts remains a challenge. Here, we present SQANTI-SIM, a versatile tool that wraps around popular long-read simulators to allow precise management of transcript novelty based on the structural categories defined by SQANTI3.

SQANTI-SIM: a simulator of controlled transcript novelty for lrRNA-seq benchmark.

Long-read RNA-seq has emerged as a powerful tool for transcript discovery, even in well-annotated organisms. However, assessing the accuracy of different methods in identifying annotated and novel transcripts remains a challenge. Here, we present SQANTI-SIM, a versatile utility that wraps around popular long-read simulators to allow precise management of transcript novelty based on the structural categories defined by SQANTI3.

Validation of gout diagnosis in electronic primary care medical records: A population-based study.

Objective: The main objective of the study was to see the concordance between the diagnosis of gout recorded in primary care electronic medical records and the ACR/EULAR 2015 classification criteria.

Methods: A cross-sectional study was conducted using electronic medicals records in 7 primary care centres of Barcelona. Patients' data to study clinical diagnose and management was gathered from the primary care electronic medical records of the Catalonian health institute (Institut Català de la Salut, ICS) and phone interview.

Integration of multi-omics data to elucidate keystone unknown taxa within microbialite-forming ecosystems.

Microbes continually shape Earth's biochemical and physical landscapes by inhabiting diverse metabolic niches. Despite the important role microbes play in ecosystem functioning, most microbial species remain unknown highlighting a gap in our understanding of structured complex ecosystems. To elucidate the relevance of these unknown taxa, often referred to as "microbial dark matter," the integration of multiple high throughput sequencing technologies was used to evaluate the co-occurrence and connectivity of all microbes within the community.

SQANTI3: curation of long-read transcriptomes for accurate identification of known and novel isoforms.

The emergence of long-read RNA sequencing (lrRNA-seq) has provided an unprecedented opportunity to analyze transcriptomes at isoform resolution. However, the technology is not free from biases, and transcript models inferred from these data require quality control and curation. In this study, we introduce SQANTI3, a tool specifically designed to perform quality analysis on transcriptomes constructed using lrRNA-seq data.

Identification of food and nutrient components as predictors of colonization.

A previous double-blind, randomized clinical trial of 42 healthy individuals conducted with N6.2 found that the probiotic's mechanistic tryptophan pathway was significantly modified when the data was stratified based on the individuals' lactic acid bacteria (LAB) stool content. These results suggest that confounding factors such as dietary intake which impact stool LAB content may affect the response to the probiotic treatment.

Differences in uterine and serum metabolome associated with metritis in dairy cows.

Objectives were to evaluate differences in the uterine and serum metabolomes associated with metritis in dairy cows. Vaginal discharge was evaluated using a Metricheck device (Simcro) at 5, 7, and 11 d in milk (DIM; herd 1) or 4, 6, 8, 10, and 12 DIM (herd 2). Cows with reddish or brownish, watery, and fetid discharge were diagnosed with metritis (n = 24).

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases: multicentre study of 80 patients.

Objectives: To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID).

Methods: Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis.

New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-β2.

Background: JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear.

Results: Here, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-β2 genes.

Extreme In Situ Liver Surgery Under Total Vascular Exclusion with Right Hepatic Vein and Inferior Vena Cava Grafts for an Intrahepatic Cholangiocarcinoma.

In this multimedia article, we demonstrate an extreme in situ liver surgery under total vascular exclusion with right hepatic vein and inferior vena cava grafts for an intrahepatic cholangiocarcinoma in a centre with experience in highly complex hepatobiliary surgery and liver transplantation. This surgical approach after neoadjuvant chemotherapy provides an opportunity for surgical salvage in patients with large tumors invading the hepatocaval confluence. This patient was considered unresectable at another hospital and referred to our unit.

Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers.

Obesity and elevated circulating lipids may impair metabolism by disrupting the molecular circadian clock. We tested the hypothesis that lipid overload may interact with the circadian clock and alter the rhythmicity of gene expression through epigenomic mechanisms in skeletal muscle. Palmitate reprogrammed the circadian transcriptome in myotubes without altering the rhythmic mRNA expression of core clock genes.

Frailty and Hospitalization Burden in Patients With Chronic Heart Failure.

Frailty is associated with increased mortality and hospitalizations in patients with heart failure (HF). However, there is little evidence regarding the burden of morbidity. In this study, we aimed to assess the association between frailty and recurrent all-cause HF hospitalizations in patients with stable chronic HF.