Pathogenic mitochondrial DNA variants are associated with response to anti-VEGF therapy in ovarian cancer PDX models.

Background: Mitochondrial DNA (mtDNA) pathogenic variants have been reported in several solid tumors including ovarian cancer (OC), the most lethal gynecologic malignancy, and raised interest as they potentially induce mitochondrial dysfunction and rewiring of cellular metabolism. Despite advances in recent years, functional characterization of mtDNA variants in cancer and their possible modulation of drug response remain largely uncharted.

Methods: Here, we characterized mtDNA variants in OC patient derived xenografts (PDX) and investigated their impact on cancer cells at multiple levels.

BioID-based intact cell interactome of the Kv1.3 potassium channel identifies a Kv1.3-STAT3-p53 cellular signaling pathway.

Kv1.3 is a multifunctional potassium channel implicated in multiple pathologies, including cancer. However, how it is involved in disease progression is not fully clear.

Interactomic exploration of LRRC8A in volume-regulated anion channels.

Ion channels are critical in enabling ion movement into and within cells and are important targets for pharmacological interventions in different human diseases. In addition to their ion transport abilities, ion channels interact with signalling and scaffolding proteins, which affects their function, cellular positioning, and links to intracellular signalling pathways. The study of "channelosomes" within cells has the potential to uncover their involvement in human diseases, although this field of research is still emerging.

Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.

Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon.

A pan-cancer landscape of pathogenic somatic copy number variations.

Objective: Copy number variations (CNVs) play crucial roles in physiological and pathological processes, including cancer. However, the functional implications of somatic CNVs in tumor progression and evolution remain unclear. This study focuses on identifying CNV alterations with high pathogenic potential that drive and sustain tumorigenesis, distinguishing them from passenger alterations that accumulate during tumor growth.

Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors.

Purpose: Patient-derived cancer cell lines can be very useful to investigate genetic as well as epigenetic mechanisms of transformation and to test new drugs. In this multi-centric study, we performed genomic and transcriptomic characterization of a large set of patient-derived glioblastoma (GBM) stem-like cells (GSCs).

Methods: 94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and trascriptome analysis, respectively.

signifinder enables the identification of tumor cell states and cancer expression signatures in bulk, single-cell and spatial transcriptomic data.

Over the last decade, many studies and some clinical trials have proposed gene expression signatures as a valuable tool for understanding cancer mechanisms, defining subtypes, monitoring patient prognosis, and therapy efficacy. However, technical and biological concerns about reproducibility have been raised. Technical reproducibility is a major concern: we currently lack a computational implementation of the proposed signatures, which would provide detailed signature definition and assure reproducibility, dissemination, and usability of the classifier.

Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca accumulation in spinobulbar muscular atrophy skeletal muscle.

Polyglutamine expansion in the androgen receptor (AR) causes spinobulbar muscular atrophy (SBMA). Skeletal muscle is a primary site of toxicity; however, the current understanding of the early pathological processes that occur and how they unfold during disease progression remains limited. Using transgenic and knock-in mice and patient-derived muscle biopsies, we show that SBMA mice in the presymptomatic stage develop a respiratory defect matching defective expression of genes involved in excitation-contraction coupling (ECC), altered contraction dynamics, and increased fatigue.

Spatial compartmentalization of signaling imparts source-specific functions on secreted factors.

Efficient regeneration requires multiple cell types acting in coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profile the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. We generate a time-resolved computational model of interactions and identify VEGFA-driven endothelial engagement as a key differentiating feature in models of successful and failed regeneration.

Hydrogen peroxide induced by nerve injury promotes axon regeneration via connective tissue growth factor.

Regeneration of the neuromuscular junction (NMJ) leverages on extensive exchange of factors released from motor axon terminals (MATs), muscle fibers and perisynaptic Schwann cells (PSCs), among which hydrogen peroxide (HO) is a major pro-regenerative signal. To identify critical determinants of NMJ remodeling in response to injury, we performed temporal transcriptional profiling of NMJs from 2 month-old mice during MAT degeneration/regeneration, and cross-referenced the differentially expressed genes with those elicited by HO in SCs. We identified an enrichment in extracellular matrix (ECM) transcripts, including Connective Tissue Growth Factor (Ctgf), which is usually expressed during development.

A comprehensive investigation of histotype-specific microRNA and their variants in Stage I epithelial ovarian cancers.

isomiRs, the sequence-variants of microRNA, are known to be tissue and cell type specific but their physiological role is largely unknown. In our study, we explored for the first time the expression of isomiRs across different Stage I epithelial ovarian cancer (EOC) histological subtypes, in order to shed new light on their biological role in tumor growth and progression. In a multicentric retrospective cohort of tumor biopsies (n = 215) we sequenced small RNAs finding 971 expressed miRNAs, 64% of which are isomiRs.

benchdamic: benchmarking of differential abundance methods for microbiome data.

Summary: Recently, an increasing number of methodological approaches have been proposed to tackle the complexity of metagenomics and microbiome data. In this scenario, reproducibility and replicability have become two critical issues, and the development of computational frameworks for the comparative evaluations of such methods is of utmost importance. Here, we present benchdamic, a Bioconductor package to benchmark methods for the identification of differentially abundant taxa.

A thorough annotation of the krill transcriptome offers new insights for the study of physiological processes.

The krill species Euphausia superba plays a critical role in the food chain of the Antarctic ecosystem. Significant changes in climate conditions observed in the Antarctic Peninsula region in the last decades have already altered the distribution of krill and its reproductive dynamics. A deeper understanding of the adaptation capabilities of this species is urgently needed.

Copy number alterations in stage I epithelial ovarian cancer highlight three genomic patterns associated with prognosis.

Background: Stage I epithelial ovarian cancer (EOC) encompasses five histologically different subtypes of tumors confined to the ovaries with a generally favorable prognosis. Despite the intrinsic heterogeneity, all stage I EOCs are treated with complete resection and adjuvant therapy in most of the cases. Owing to the lack of robust prognostic markers, this often leads to overtreatment.

Detecting differentially expressed circular RNAs from multiple quantification methods using a generalized linear mixed model.

Finding differentially expressed circular RNAs (circRNAs) is instrumental to understanding the molecular basis of phenotypic variation between conditions linked to circRNA-involving mechanisms. To date, several methods have been developed to identify circRNAs, and combining multiple tools is becoming an established approach to improve the detection rate and robustness of results in circRNA studies. However, when using a consensus strategy, it is unclear how circRNA expression estimates should be considered and integrated into downstream analysis, such as differential expression assessment.

Zebrafish Mutant Lines Reveal the Interplay between and in the GC-Dependent Regulation of Gene Transcription.

Glucocorticoids mainly exert their biological functions through their cognate receptor, encoded by the gene. Here, we analysed the glucocorticoids mechanism of action taking advantage of the availability of different zebrafish mutant lines for their receptor. The differences in gene expression patterns between the zebrafish knock-out and the mutant line, in which a point mutation prevents binding of the receptor to the hormone-responsive elements, reveal an intricate network of GC-dependent transcription.

NewWave: a scalable R/Bioconductor package for the dimensionality reduction and batch effect removal of single-cell RNA-seq data.

Summary: We present NewWave, a scalable R/Bioconductor package for the dimensionality reduction and batch effect removal of single-cell RNA sequencing data. To achieve scalability, NewWave uses mini-batch optimization and can work with out-of-memory data, enabling users to analyze datasets with millions of cells.

Availability And Implementation: NewWave is implemented as an open-source R package available through the Bioconductor project at https://bioconductor.

The power of word-frequency-based alignment-free functions: a comprehensive large-scale experimental analysis.

Motivation: Alignment-free (AF) distance/similarity functions are a key tool for sequence analysis. Experimental studies on real datasets abound and, to some extent, there are also studies regarding their control of false positive rate (Type I error). However, assessment of their power, i.

Circulating miR-185-5p as a Potential Biomarker for Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial fibro-fatty replacement, arrhythmias and risk of sudden death. Its diagnosis is challenging and often it is achieved after disease onset or postmortem. In this study, we sought to identify circulating microRNAs (miRNAs) differentially expressed in ARVC patients compared to healthy controls.

MyoData: An expression knowledgebase at single cell/nucleus level for the discovery of coding-noncoding RNA functional interactions in skeletal muscle.

Non-coding RNAs represent the largest part of transcribed mammalian genomes and prevalently exert regulatory functions. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) can modulate the activity of each other. Skeletal muscle is the most abundant tissue in mammals.