Novel Assignment of Gene Markers to Hematological and Immune Cells Based on Single-Cell Transcriptomics.

There are many different cells that perform highly specialized functions in the human hematological and immune systems. Due to the relevance of their activity, in this work we investigated the cell types and subtypes that form this complex system, using single-cell RNA sequencing (scRNA-seq) to dissect and assess the markers that best define each cell population. We first developed an optimized computational workflow for analyzing large scRNA-seq datasets.

Assessment of Humoral Response at SARS-CoV-2 Infection by Multipronged Functional Proteomics Approaches.

In the past decade, a major goal in biomedical research has been to understand why individuals differ in disease susceptibility, disease dynamics, and progression. In many pathologies, this variability stems from evolved immune mechanisms that resist inflammatory stress from various diseases that have been encountered throughout life. These may provide advantages against other diseases, reduce comorbidities, and enhance longevity.

Cross-species regulatory network analysis identifies FOXO1 as a driver of ovarian follicular recruitment.

The transcriptional regulation of gene expression in the latter stages of follicular development in laying hen ovarian follicles is not well understood. Although differentially expressed genes (DEGs) have been identified in pre-recruitment and pre-ovulatory stages, the master regulators driving these DEGs remain unknown. This study addresses this knowledge gap by utilizing Master Regulator Analysis (MRA) combined with the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) for the first time in laying hen research to identify master regulators that are controlling DEGs in pre-recruitment and pre-ovulatory phases.

The ISCB competency framework v. 3: a revised and extended standard for bioinformatics education and training.

Motivation: Developing competency in the broad area of bioinformatics is challenging globally, owing to the breadth of the field and the diversity of its audiences for education and training. Course design can be facilitated by the use of a competency framework-a set of competency requirements that define the knowledge, skills and attitudes needed by individuals in (or aspiring to be in) a particular profession or role. These competency requirements can help to define curricula as they can inform both the content and level to which competency needs to be developed.

Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.

Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through a common linker tetrasaccharide. In the extracellular space, they are involved in the regulation of cell communication, assuring development and homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated to defects in some of them.

Novel Gene Biomarkers Specific to Human Mesenchymal Stem Cells Isolated from Bone Marrow.

In this paper, we present a comparative analysis of the transcriptomic profile of three different human cell types: hematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stem cells (MSCs) and fibroblasts (FIBs). The work aims to identify unique genes that are differentially expressed as specific markers of bone marrow-derived MSCs, and to achieve this undertakes a detailed analysis of three independent datasets that include quantification of the global gene expression profiles of three primary cell types: HSCs, MSCs and FIBs. A robust bioinformatics method, called , is used to assess the specific association between one or more genes expressed in a sample and the outcome variable, that is, the 'cell type' provided as a single univariate response.

Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human.

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects.

Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours.

The consensus molecular subtypes (CMSs) classification of colorectal cancer (CRC) is a system for patient stratification that can be potentially applied to therapeutic decisions. Hakai (CBLL1) is an E3 ubiquitin-ligase that induces the ubiquitination and degradation of E-cadherin, inducing epithelial-to-mesenchymal transition (EMT), tumour progression and metastasis. Using bioinformatic methods, we have analysed CBLL1 expression on a large integrated cohort of primary tumour samples from CRC patients.

Germline variants in early and late-onset Brazilian prostate cancer patients.

Background: The median age for Prostate Cancer (PCa) diagnosis is 66 years, but 10% are diagnosed before 55 years. Studies on early-onset PCa remain both limited and controversial. This investigation sought to identify and characterize germline variants within Brazilian PCa patients classified as either early or later onset disease.

Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.

Background: Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) share phenotypic and molecular commonalities, including the fact that they can be caused by mutations in ubiquitous proteins involved in RNA metabolism, namely SMN, TDP-43 and FUS. Although this suggests the existence of common disease mechanisms, there is currently no model to explain the resulting motor neuron dysfunction. In this work we generated a parallel set of Drosophila models for adult-onset RNAi and tagged neuronal expression of the fly orthologues of the three human proteins, named Smn, TBPH and Caz, respectively.

METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer.

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-methylguanosine (mG) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of mG tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments.

Comparative Analysis of Cell Mixtures Deconvolution and Gene Signatures Generated for Blood, Immune and Cancer Cells.

In the last two decades, many detailed full transcriptomic studies on complex biological samples have been published and included in large gene expression repositories. These studies primarily provide a bulk expression signal for each sample, including multiple cell-types mixed within the global signal. The cellular heterogeneity in these mixtures does not allow the activity of specific genes in specific cell types to be identified.

Whole-Genome Doubling as a source of cancer: how, when, where, and why?

Chromosome instability is a well-known hallmark of cancer, leading to increased genetic plasticity of tumoral cells, which favors cancer aggressiveness, and poor prognosis. One of the main sources of chromosomal instability are events that lead to a Whole-Genome Duplication (WGD) and the subsequently generated cell polyploidy. In recent years, several studies showed that WGD occurs at the early stages of cell transformation, which allows cells to later become aneuploid, thus leading to cancer progression.

Identification of a gene expression signature associated with breast cancer survival and risk that improves clinical genomic platforms.

Motivation: Modern genomic technologies allow us to perform genome-wide analysis to find gene markers associated with the risk and survival in cancer patients. Accurate risk prediction and patient stratification based on robust gene signatures is a key path forward in personalized treatment and precision medicine. Several authors have proposed the identification of gene signatures to assign risk in patients with breast cancer (BRCA), and some of these signatures have been implemented within commercial platforms in the clinic, such as Oncotype and Prosigna.

Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells.

Background: Eltrombopag (EP) is a small molecule that acts directly on hematopoietic stem cells (HSCs) and megakaryocytes to stimulate the hematopoietic process. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators.

Objectives: We aimed to determine whether EP has any effect on MSC function and properties (especially on their hematopoietic-supporting ability) and if so, what changes (e.

Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease.

Protein-protein interactions (PPI) play an essential role in the biological processes that occur in the cell. Therefore, the dissection of PPI networks becomes decisive to model functional coordination and predict pathological de-regulation. Cellular networks are dynamic and proteins display varying roles depending on the tissue-interactomic context.

Correction: Ten simple rules for organizing a bioinformatics training course in low- and middle-income countries.

[This corrects the article DOI: 10.1371/journal.pcbi.

SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS.

Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which is one of the major complications in COVID-19 patients. Dysregulation of the immune system and imbalances in cytokine release and immune cell activation are involved in SARS-CoV-2 infection. Here, the inflammatory, antigen, and auto-immune profile of patients presenting COVID-19-associated severe ARDS has been analyzed using functional proteomics approaches.

Transient Inhibition of the JAK/STAT Pathway Prevents B-ALL Development in Genetically Predisposed Mice.

Unlabelled: Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Preclinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens.

A Gene Signature Derived from the Loss of CDKN1A (p21) Is Associated with CMS4 Colorectal Cancer.

The epithelial-mesenchymal transition (EMT) is associated with tumor aggressiveness and increased invasion, migration, metastasis, angiogenesis, and drug resistance. Although the HCT116 p21-/- cell line is well known for its EMT-associated phenotype, with high Vimentin and low E-cadherin protein levels, the gene signature of this rather intermediate EMT-like cell line has not been determined so far. In this work, we present a robust molecular and bioinformatics analysis, to reveal the associated gene expression profile and its correlation with different types of colorectal cancer tumors.