Applicazione di un algoritmo d’apprendimento basato su sistemi fuori dall’equilibrio a dati di Genome Wide Association

Il fenomeno dell’apprendimento può essere studiato attraverso metodiche di Meccanica Statistica. A partire dalle Neural Networks è possibile descrivere il problema dell'apprendimento mediante un sistema di spin interagenti. Usando una descrizione all’equilibrio del sistema e sotto opportune condizioni, tale problema si dimostra computazionalmente complesso. Tuttavia, esistono algoritmi euristici in grado di risolvere lo stesso problema efficacemente. Si dimostra che questa apparente inconsistenza è dovuta al fatto che lo spazio delle soluzioni degli algoritmi euristici non coincida con quello atteso all’equilibrio. Utilizzando una distribuzione fuori dall’equilibrio è possibile realizzare l’algoritmo replicated focusing Belief Propagation (rfBP), i cui risultati in termini di performance computazionali e di natura delle soluzioni sono in linea con i risultati degli algoritmi euristici. Questo lavoro evidenzia come l’utilizzo integrato di modelli a Spin-Glass, grafi e Neural Networks siano in grado di creare una base teorica solida per lo sviluppo di algoritmi di machine learning originali e innovativi. Questo lavoro, inoltre, introduce una nuova libreria di C++ ottimizzata per il calcolo parallelo dell’algoritmo rfBP e applica tale algoritmo su dati di Genome Wide Association. Sono stati considerati campioni di genomi del batterio Salmonella, ospitati in diversi animali, ed è stato effettutato il training dell’algoritmo rfBP sull’insorgenza di mutazioni (Single Nucleotide Polymorphism, SNP), nel tentativo di determinare l’animale da cui essi sono stati ospitati. L’obiettivo di questa applicazione è capire come i genomi dei batteri siano influenzati dal proprio ospite animale e se è possibile evidenziare delle caratteristiche che permettano di risalire dalla sequenza di SNPs all’ospite. Questo lavoro mostra che l’algoritmo rfBP produce, su tali sequenze di SNPs, performance comparabili e superiori a quelli ricavati con le più comuni tecniche di Machine Learning

Intraspecies characterization of bacteria via evolutionary modeling of protein domains

The ability to detect and characterize bacteria within a biological sample is crucial for the monitoring of infections and epidemics, as well as for the study of human health and its relationship with commensal microorganisms. To this aim, a commonly used technique is the 16S rRNA gene targeted sequencing. PCR-amplified 16S sequences derived from the sample of interest are usually clustered into the so-called Operational Taxonomic Units (OTUs) based on pairwise similarities. Then, representative OTU sequences are compared with reference (human-made) databases to derive their phylogeny and taxonomic classification. Here, we propose a new reference-free approach to define the phylogenetic distance between bacteria based on protein domains, which are the evolving units of proteins. We extract the protein domain profiles of 3368 bacterial genomes and we use an ecological approach to model their Relative Species Abundance distribution. Based on the model parameters, we then derive a new measurement of phylogenetic distance. Finally, we show that such model-based distance is capable of detecting differences between bacteria in cases in which the 16S rRNA-based method fails, providing a possibly complementary approach , which is particularly promising for the analysis of bacterial populations measured by shotgun sequencing

A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Background Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. Methods In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Dusseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. Findings The study included 7792 (58middot7%) men and 5492 (41middot3%) women. 10 906 (82middot1%) patients were White, and race was not reported for 2378 (17middot9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0middot0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0middot0062 in the IWG-PM cohort; IDH2 p<0middot0001 in EuroMDS vs p=0middot042 in IWG-PM; TET2 p=0middot031 vs p=0middot035; U2AF1 p=0middot033 vs p<0middot0001) and mutations in two genes were enriched in women (DNMT3A p<0middot0001 in EuroMDS vs p=0middot011 in IWG-PM; TP53 p=0middot030 vs p=0middot037). Additionally, sex biases were observed in co-mutational pathways of founding genomic lesions (splicing-related genes, predominantly in men, p<0middot0001 in both the EuroMDS and IWG-PM cohorts), in DNA methylation (predominantly in men, p=0middot046 in EuroMDS vs p<0middot0001 in IWG-PM), and TP53 mutational pathways (predominantly in women, p=0middot0073 in EuroMDS vs p<0middot0001 in IWG-PM). In the retrospective EuroMDS cohort, men had worse median overall survival (81middot3 months, 95% CI 70middot4-95middot0 in men vs 123middot5 months, 104middot5-127middot5 in women; hazard ratio [HR] 1middot40, 95% CI 1middot26-1middot52; p<0middot0001). This result was confirmed in the prospective validation cohorts (median overall survival was 54middot7 months, 95% CI 52middot4-59middot1 in men vs 74middot4 months, 69middot3-81middot2 in women; HR 1middot30, 95% CI 1middot23-1middot35; p<0middot0001 in the GEMSD MDS registry; 40middot0 months, 95% CI 33middot4-43middot7 in men vs 54middot2 months, 38middot6-63middot8 in women; HR 1middot23, 95% CI 1middot08-1middot36; p<0middot0001 in the Dusseldorf MDS registry). We developed new personalised prognostic tools that included sex information (the sex-informed prognostic scoring system and the sex-informed genomic scoring system). Sex maintained independent prognostic power in all prognostic systems; the highest performance was observed in the model that included both sex and genomic information. A five-to-five mapping between the IPSS-R and new score categories resulted in the re-stratification of 871 (43middot0%) of 2025 patients from the EuroMDS cohort and 1003 (42middot0%) of 2387 patients from the IWG-PM cohort by using the sex-informed prognostic scoring system, and of 1134 (56middot0%) patients from the EuroMDS cohort and 1265 (53middot0%) patients from the IWG-PM cohort by using the sex-informed genomic scoring system. We created a web portal that enables outcome predictions based on a sex-informed personalised approach. Interpretation Our results suggest that a sex-informed approach can improve the personalised decision making process in patients with myelodysplastic syndromes and should be considered in the design of clinical trials including low-risk patients. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved

Xavier Barral i Altet, Guido Dall’Olio e Daniele Manacorda discutono "Storie per tutti" / Xavier Barral i Altet, Guido Dall’Olio and Daniele Manacorda talk about “Storie per tutti” (Stories for everyone)

 Si pubblica qui, in una versione rielaborata dagli autori, il testo degli interventi di Xavier Barral i Altet, Guido Dall’Olio e Daniele Manacorda, proposti il 5 giugno 2014 in occasione della presentazione presso la Biblioteca di Storia moderna e contemporanea di Roma del numero de «Il Capitale culturale. Studies on the Value of Cultural Heritage» dedicato al rapporto fra ricerca e diffusione del sapere.    We publish here the speeches, reviewed by the authors Xavier Barrall i Altet, Guido Dall’Olio and Daniele Manacorda, presented in June, 5 2014 at the Biblioteca di Storia moderna e contemporanea in Roma for the monographic issue of «Il Capitale culturale. Studies on the Value of Cultural Heritage» dedicated to the relation between the research and the diffusion of knowledge.   

The BovMAS Consortium: investigation of bovine chromosome 14 for quantitative trait loci affecting milk production and quality traits in the Italian Hoilstein Friesian breed

Many studies have demonstrated that quantitative trait loci (QTL) can be identified and mapped in commercial dairy cattle populations using genetic markers in daughter and granddaughter designs.The final objective of these studies is to identify genes or markers that can be used in breeding schemes via marker assisted selection (MAS)

Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography-tandem mass spectrometry

BACKGROUND: Men with Klinefelter syndrome (KS) show hypergonadotropic hypogonadism, but the pathogenesis of hypotestosteronemia remains unclear. Testicular steroidogenesis in KS men was evaluated over three decades ago after human chorionic gonadotropin (hCG) stimulation, but inconclusive results were obtained. Intriguingly, some recent studies show increased intratesticular testosterone concentrations in men with KS. OBJECTIVE: To analyze serum steroid profile, as a proxy of testicular steroidogenesis, after hCG stimulation in KS compared with control men. DESIGN: A prospective, longitudinal, case-control, clinical trial. METHODS: Thirteen KS patients (36±9 years) not receiving testosterone (TS) replacement therapy and 12 eugonadic controls (32±8 years) were enrolled. Serum steroids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline and for five consecutive days after intramuscular injection of 5000IU hCG. RESULTS: Progesterone (P), 17-hydroxyprogesterone (17OHP), TS, and estradiol (E2) showed a significant increase (P<0.001) after hCG stimulation in both groups. On the contrary, androstenedione (AS) and dehydroepiandrosterone did not increase after hCG stimulation. The 17OHP/P ratio increased in both groups (P<0.001), the TS/AS ratio (17β-hydroxysteroid dehydrogenase type 3 (17βHSD3) activity) did not increase after hCG in any group, and the E2/TS ratio (aromatase activity) increased significantly in both groups (P=0.009 in KS and P<0.001 in controls). Luteinizing hormone decreased after hCG in both groups (P=0.014 in KS and P<0.001 in controls), whereas follicle-stimulating hormone decreased only in control men (P<0.001). CONCLUSION: This study demonstrates for the first time using LC-MS/MS that Leydig cells of KS men are able to respond to hCG stimulation and that the first steps of steroidogenesis are fully functional. However, the TS production in KS men is impaired, possibly related to reduced hydroxysteroid deydrogenase activity due to an unfavorable intratesticular metabolic state

I demoni di Napoli. Naturale, preternaturale, sovrannaturale a Napoli e nell'Europa di età moderna

La possessione diabolica e l'arte esorcistica, le apparizioni e il culto dei santi, la medicina dotta e i rimedi popolari, il sonnambulism o e lo spiritismo: sono mappe di un percorso all'interno del "meraviglioso" napoletano di età moderna, presentato nelle sue diverse sfaccettature