DDGemb: predicting protein stability change upon single- and multi-point variations with embeddings and deep learning.

Motivation: The knowledge of protein stability upon residue variation is an important step for functional protein design and for understanding how protein variants can promote disease onset. Computational methods are important to complement experimental approaches and allow a fast screening of large datasets of variations.

Results: In this work we present DDGemb, a novel method combining protein language model embeddings and transformer architectures to predict protein ΔΔG upon both single- and multi-point variations.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Assessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges.

Recent thermodynamic and functional studies have been conducted to evaluate the impact of amino acid substitutions on Calmodulin (CaM). The Critical Assessment of Genome Interpretation (CAGI) data provider at University of Verona (Italy) measured the melting temperature (T) and the percentage of unfolding (%unfold) of a set of CaM variants (CaM challenge dataset). Thermodynamic measurements for the equilibrium unfolding of CaM were obtained by monitoring far-UV Circular Dichroism as a function of temperature.

Serological evidence of sarbecovirus exposure along Sunda pangolin trafficking pathways.

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Although it is unconfirmed whether pangolins or other traded wildlife served as intermediate hosts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the trafficking of pangolins presents a clear risk for transmission of viruses with zoonotic and epizootic potential regardless. We have investigated the origins of pangolin carcasses seized in Hong Kong and have evaluated their potential exposure to SARSr-CoVs, other coronaviruses, and paramyxoviruses, aiming to address a gap in our knowledge with regard to the role of wildlife trade in the maintenance and emergence of pathogens with zoonotic and epizootic potential.

Hyperosmotic Stress Induces the Expression of Organic Osmolyte Transporters in Porcine Intestinal Cells and Betaine Exerts a Protective Effect on the Barrier Function.

The porcine intestinal epithelium plays a fundamental role as a defence interface against pathogens. Its alteration can cause severe inflammatory conditions and diseases. Hyperosmotic stress under physiological conditions and upon pathogen challenge can cause malabsorption.

Testing the Capability of Embedding-Based Alignments on the GST Superfamily Classification: The Role of Protein Length.

In order to shed light on the usage of protein language model-based alignment procedures, we attempted the classification of Glutathione S-transferases (GST; EC 2.5.1.

Rosette-forming multicentric B-cell lymphoma in a giant panda.

Literature covering diseases of the giant panda () is either in Chinese or focuses on infectious agents. Here we describe the clinical signs, gross and microscopic findings, and immunohistochemistry results of a B-cell lymphoma in multiple organs of a 35-y-old captive male giant panda. The animal was euthanized because of prolonged anorexia and vomiting.

E-pRSA: Embeddings Improve the Prediction of Residue Relative Solvent Accessibility in Protein Sequence.

Knowledge of the solvent accessibility of residues in a protein is essential for different applications, including the identification of interacting surfaces in protein-protein interactions and the characterization of variations. We describe E-pRSA, a novel web server to estimate Relative Solvent Accessibility values (RSAs) of residues directly from a protein sequence. The method exploits two complementary Protein Language Models to provide fast and accurate predictions.

Whole Genome Sequence Analysis of Brucella spp. from Human, Livestock, and Wildlife in South Africa.

Brucellosis is an economically important zoonotic disease affecting humans, livestock, and wildlife health globally and especially in Africa. Brucella abortus and B. melitensis have been isolated from human, livestock (cattle and goat), and wildlife (sable) in South Africa (SA) but with little knowledge of the population genomic structure of this pathogen in SA.

Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.

Critical evaluation of computational tools for predicting variant effects is important considering their increased use in disease diagnosis and driving molecular discoveries. In the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, a dataset of 28 STK11 rare variants (27 missense, 1 single amino acid deletion), identified in primary non-small cell lung cancer biopsies, was experimentally assayed to characterize computational methods from four participating teams and five publicly available tools. Predictors demonstrated a high level of performance on key evaluation metrics, measuring correlation with the assay outputs and separating loss-of-function (LoF) variants from wildtype-like (WT-like) variants.

Monitoring the world-oldest zoo-housed male giant panda (Ailuropoda melanoleuca): A case-study on pathway utilization.

Habitat use monitoring is necessary for a comprehensive understanding of the biological and psychological requirements of animals under human care, facilitating improved exhibit designs and promoting animal welfare. Current studies focused on the space use of the exhibit while limited studies examined the pathway use of the zoo-housed animals. This study aimed to investigate the habitat use of An An, the world-oldest male giant panda (Ailuropoda melanoleuca) at Ocean Park Hong Kong using a pathway utilization monitoring method.

Critical assessment of missense variant effect predictors on disease-relevant variant data.

Regular, systematic, and independent assessment of computational tools used to predict the pathogenicity of missense variants is necessary to evaluate their clinical and research utility and suggest directions for future improvement. Here, as part of the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, we assess missense variant effect predictors (or variant impact predictors) on an evaluation dataset of rare missense variants from disease-relevant databases. Our assessment evaluates predictors submitted to the CAGI6 Annotate-All-Missense challenge, predictors commonly used by the clinical genetics community, and recently developed deep learning methods for variant effect prediction.

Experimental implementation of a quantum zero-knowledge proof for user authentication.

A new interactive quantum zero-knowledge protocol for identity authentication implementable in currently available quantum cryptographic devices is proposed and demonstrated. The protocol design involves a verifier and a prover knowing a pre-shared secret, and the acceptance or rejection of the proof is determined by the quantum bit error rate. It has been implemented in modified Quantum Key Distribution devices executing two fundamental cases.

Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.

Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the () gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models.

Alpha&ESMhFolds: A Web Server for Comparing AlphaFold2 and ESMFold Models of the Human Reference Proteome.

We develop a novel database Alpha&ESMhFolds which allows the direct comparison of AlphaFold2 and ESMFold predicted models for 42,942 proteins of the Reference Human Proteome, and when available, their comparison with 2,900 directly associated PDB structures with at least a structure to sequence coverage of 70%. Statistics indicate that good quality models tend to overlap with a TM-score >0.6 as long as some PDB structural information is available.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

Background: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating.

Early onset absence epilepsy of childhood: Epidemiologic data, treatment and outcome in a sample of 56 patients born between 2000 and 2018.

Purpose: The aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology.

Methods: We carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset.

Dispersion of antimicrobial resistant bacteria in pig farms and in the surrounding environment.

Background: Antimicrobial resistance has been identified as a major threat to global health. The pig food chain is considered an important source of antimicrobial resistance genes (ARGs). However, there is still a lack of knowledge on the dispersion of ARGs in pig production system, including the external environment.

Short-chain fatty acids modulate the IPEC-J2 cell response to pathogenic E. coli LPS-activated PBMC.

Intestinal disorders can affect pigs of any age, especially when animals are young and more susceptible to infections and environmental stressors. For instance, pathogenic E. coli can alter intestinal functions, thus leading to altered nutrient adsorption by interacting with local cells through lipopolysaccharide (LPS).

[Franco Basaglia: the body and the corporality of the encounter.].

On the centenary of the birth of Franco Basaglia - Italian psychiatrist and neurologist - it is incumbent upon us to question the ways in which Basaglia can critically illuminate or help us interpret the social uncertainty in which we are living. Many important contributions have enriched our knowledge of Basaglia's work in recent months. He was a modern practical intellectual, in the Gramscian sense, where the authentic intellectual moves from the real needs of the masses and seeks their solution from the given historical situation, recomposing it in the more general course of the world.

CoCoNat: A Deep Learning-Based Tool for the Prediction of Coiled-coil Domains in Protein Sequences.

Coiled-coil domains (CCDs) are structural motifs observed in proteins in all organisms that perform several crucial functions. The computational identification of CCD segments over a protein sequence is of great importance for its functional characterization. This task can essentially be divided into three separate steps: the detection of segment boundaries, the annotation of the heptad repeat pattern along the segment, and the classification of its oligomerization state.

Routes of dispersion of antibiotic resistance genes from the poultry farm system.

Poultry farms are hotspots for the development and spread of antibiotic resistance genes (ARGs), due to high stocking densities and extensive use of antibiotics, posing a threat of spread and contagion to workers and the external environment. Here, we applied shotgun metagenome sequencing to characterize the gut microbiome and resistome of poultry, workers and their households - also including microbiomes from the internal and external farm environment - in three different farms in Italy during a complete rearing cycle. Our results highlighted a relevant overlap among the microbiomes of poultry, workers, and their families (gut and skin), with clinically relevant ARGs and associated mobile elements shared in both poultry and human samples.

MultifacetedProtDB: a database of human proteins with multiple functions.

MultifacetedProtDB is a database of multifunctional human proteins deriving information from other databases, including UniProt, GeneCards, Human Protein Atlas (HPA), Human Phenotype Ontology (HPO) and MONDO. It collects under the label 'multifaceted' multitasking proteins addressed in literature as pleiotropic, multidomain, promiscuous (in relation to enzymes catalysing multiple substrates) and moonlighting (with two or more molecular functions), and difficult to be retrieved with a direct search in existing non-specific databases. The study of multifunctional proteins is an expanding research area aiming to elucidate the complexities of biological processes, particularly in humans, where multifunctional proteins play roles in various processes, including signal transduction, metabolism, gene regulation and cellular communication, and are often involved in disease insurgence and progression.