Quantifying human performance in chess

From sports to science, the recent availability of large-scale data has allowed to gain insights on the drivers of human innovation and success in a variety of domains. Here we quantify human performance in the popular game of chess by leveraging a very large dataset comprising of over 120 million games between almost 1 million players. We find that individuals encounter hot streaks of repeated success, longer for beginners than for expert players, and even longer cold streaks of unsatisfying performance. Skilled players can be distinguished from the others based on their gaming behaviour. Differences appear from the very first moves of the game, with experts tending to specialize and repeat the same openings while beginners explore and diversify more. However, experts experience a broader response repertoire, and display a deeper understanding of different variations within the same line. Over time, the opening diversity of a player tends to decrease, hinting at the development of individual playing styles. Nevertheless, we find that players are often not able to recognize their most successful openings. Overall, our work contributes to quantifying human performance in competitive settings, providing a first large-scale quantitative analysis of individual careers in chess, helping unveil the determinants separating elite from beginner performance.Comment: 8 pages, 5 figure

A Spatiotemporal Gamma Shot Noise Cox Process

A new discrete-time shot noise Cox process for spatiotemporal data is proposed. The random intensity is driven by a dependent sequence of latent gamma random measures. Some properties of the latent process are derived, such as an autoregressive representation and the Laplace functional. Moreover, these results are used to derive the moment, predictive, and pair correlation measures of the proposed shot noise Cox process. The model is flexible but still tractable and allows for capturing persistence, global trends, and latent spatial and temporal factors. A Bayesian inference approach is adopted, and an efficient Markov Chain Monte Carlo procedure based on conditional Sequential Monte Carlo is proposed. An application to georeferenced wildfire data illustrates the properties of the model and inference

The physics of higher-order interactions in complex systems

Complex networks have become the main paradigm for modelling the dynamics of interacting systems. However, networks are intrinsically limited to describing pairwise interactions, whereas real-world systems are often characterized by higher-order interactions involving groups of three or more units. Higher-order structures, such as hypergraphs and simplicial complexes, are therefore a better tool to map the real organization of many social, biological and man-made systems. Here, we highlight recent evidence of collective behaviours induced by higher-order interactions, and we outline three key challenges for the physics of higher-order systems

Diagnostic Yield and Miss Rate of EndoRings in an Organized Colorectal Cancer Screening Program: the SMART (Study Methodology for ADR-Related Technology) Trial

Background and aims The add-on EndoRings has been claimed to improve adenoma detection at colonoscopy, but available data are inconsistent. When testing a new technology, parallel and crossover methodologies measure different outcomes, leaving uncertainty on their correspondence. Aims of this study were to compare the diagnostic yield and miss rate of the EndoRings for colorectal neoplasia. Methods Consecutive subjects undergoing colonoscopy after a positive fecal immunochemical test (FIT) within organized screening program in 7 Italian centers, were randomized between a parallel (EndoRings or Standard) or a crossover (EndoRings/Standard or Standard/EndoRings) methodology. Outcomes measures were the detection rates of (advanced) adenomas (A-)ADR in the parallel arms and miss rate of adenomas in the crossover arms. Results Of 958 eligible subjects, 927 (317 EndoRings; 317 Standard; 142 EndoRings/Standard; 151 Standard/Endorings) were included in the final analysis. In the parallel arms (mean ADR: 51.3%; mean AADR: 25.4%), no difference between Standard and EndoRings was found for both ADR (RR, 1.10; 95% CI, 0.95-1.28) and A-ADR (RR, 1.16; 95% CI, 0.88-1.51), as well as for the mean number of adenomas and advanced adenomas per patient (EndoRings: 1.9±1.3 and 1.0±1.2; Standard 2.1±1.5 and 1.0±1.2; p=NS for both comparisons). In the crossover arms, no difference in miss rate for adenomas between EndoRings and Standard was found at per-polyp (RR, 1.43; 95% CI, 0.97-2.10), as well as at per-patient analysis (24% vs 26%; p=0.76). Conclusions No statistically significant difference in diagnostic yield and miss rate between EndoRings and Standard colonoscopy was detected in FIT+ patients. A clinically relevant correspondence between miss and detection rates was shown, supporting a cause-effect relationship

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)