Tiziana Sanavia

University of Turin | UNITO · Department of Medical Science

Background: Sickle cell disease (SCD) is a life-threatening genetic inherited disease considered rare in the European Union (EU). Its complex mechanisms lead to highly variable clinical expression, encompassing in a majority of patients severe acute events and progressive organ damage with premature death. The lack of large datasets combining stand...

Background. Study of myeloid neoplasms (MN) has been rapidly transformed by genome characterization. Gene mutations have been reported to influence disease phenotype and risk of disease progression, and the evaluation of mutational status can provide valuable insights to improve the decision-making process. In this international study, we evaluated...

Background. In hematology, leveraging real-world multimodal data at large scale is crucial for developing personalized medicine to address unmet clinical needs, particularly for rare diseases. Generative AI in healthcare shows great promise by generating multimodal synthetic data (SD) to improve patients' diagnosis and prognosis while accelerating...

Background. Recent advancements in genome characterization have transformed the study of myelodysplastic syndromes (MDS). Accordingly, there has been a shift from traditional classification and prognostication methods, which relied mainly on morphological and clinical data, to next-generation systems that incorporate genomic features. However, gene...

Introduction: Sickle cell disease (SCD) is a hereditary disorder characterized by the production of structurally abnormal hemoglobin S (HbS) in red blood cells (RBCs). Under low oxygen saturation, HbS polymerizes, causing RBCs to deform, leading to hemolytic anemia, recurrent vaso-occlusive episodes (VOE) and organ damage. VOE are unpredictable and...

BACKGROUND. Most oncological and non-oncological hematological conditions fall under the category of rare diseases. Rare diseases present unique challenges due to the limited availability of data, which impacts diagnostic rates and the generation of clinical evidence. Overall, they constitute a public health concern, highlighting the urgent need to...

Background: Limited data exist on ultrathin-strut drug-eluting stent (ultrathin DES) performance in DES in-stent restenosis (ISR). Aims: We aimed to assess the efficacy and safety of ultrathin DES compared to thin-strut DES and drug-eluting balloons (DEB) for DES-ISR. Methods: Patients from the DEB Dragon (ClinicalTrials.gov: NCT04415216) and...

PURPOSE Rare cancers constitute over 20% of human neoplasms, often affecting patients with unmet medical needs. The development of effective classification and prognostication systems is crucial to improve the decision-making process and drive innovative treatment strategies. We have created and implemented MOSAIC, an artificial intelligence (AI)–b...

Motivation Mutational signatures are a critical component in deciphering the genetic alterations that underlie cancer development and have become a valuable resource to understand the genomic changes during tumorigenesis. Therefore, it is essential to employ precise and accurate methods for their extraction to ensure that the underlying patterns ar...

Data sharing among different institutions represents one of the major challenges in developing distributed machine learning approaches, especially when data is sensitive, such as in medical applications. Federated learning is a possible solution, but requires fast communications and flawless security. Here, we propose SYNDSURV (SYNthetic Distribute...

One of the key goals in the postgenomic era is the elucidation of the mechanisms underlying the relationship between genotype and phenotype. In particular, understanding how human genetic and somatic variations are associated with diseases is still an open problem and its solution is a crucial issue for exploiting the possibilities offered by the m...

Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship be...

Missense variation in genomes can affect protein structure stability and, in turn, the cell physiology behavior. Predicting the impact of those variations is relevant, and the best-performing computational tools exploit the protein structure information. However, most of the current protein sequence variants are unresolved, and comparative or ab in...

Background Spleen stiffness measurement (SSM) performed by transient elastography at 100 Hz is a novel technology for the evaluation of portal hypertension in advanced chronic liver disease, but technical aspects are lacking. We aimed to evaluate the intraexamination variability of SSM and to determine the best transient elastography protocol for o...

Mutational signatures are a critical component in deciphering the genetic alterations that underlie cancer development and have become a valuable resource for understanding the genomic changes that occur during tumorigenesis. In this paper, we present MUSE-XAE, a novel method for mutational signature extraction from cancer genomes using an explaina...

Background & Aims: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT)...

Federated learning initiatives in healthcare are being developed to collaboratively train predictive models without the need to centralize sensitive personal data. GenoMed4All is one such project, with the goal of connecting European clinical and -omics data repositories on rare diseases through a federated learning platform. Currently, the consort...

Bacteria respond to nutrient starvation implementing the stringent response, a stress signaling system resulting in metabolic remodeling leading to decreased growth rate and energy requirements. A well-characterized model of stringent response in Mycobacterium tuberculosis is the one induced by growth in low phosphate. The extracytoplasmic function...

Neuroblastoma is a childhood neurological tumor which affects hundreds of thousands of children worldwide, and information about its prognosis can be pivotal for patients, their families, and clinicians. One of the main goals in the related bioinformatics analyses is to provide stable genetic signatures able to include genes whose expression levels...

Background The exposome drivers are less studied than its consequences but may be crucial in identifying population subgroups with unfavourable exposures. Objectives We used three approaches to study the socioeconomic position (SEP) as a driver of the early-life exposome in Turin children of the NINFEA cohort (Italy). Methods Forty-two environmen...

An open challenge of computational and experimental biology is understanding the impact of non-synonymous DNA variations on protein function and, subsequently, human health. The effects of these variants on protein stability can be measured as the difference in the free energy of unfolding (ΔΔ G ) between the mutated structure of the protein and it...

The high cosine similarity between some single-base substitution mutational signatures and their characteristic flat profiles could suggest the presence of overfitting and mathematical artefacts. The newest version (v3.3) of the signature database available in the Catalogue Of Somatic Mutations In Cancer (COSMIC) provides a collection of 79 mutatio...

Amyotrophic lateral sclerosis (ALS) is a highly complex and heterogeneous neurodegenerative disease that affects motor neurons. Since life expectancy is relatively low, it is essential to promptly understand the course of the disease to better target the patient’s treatment. Predictive models for disease progression are thus of great interest. One...

Background: The use of Artificial Intelligence (AI) for personalized medicine has recently guided improvements in the diagnostic pathway of many diseases. The EU Project GENOMED4ALL: “Genomics and personalized Medicine for All through Artificial Intelligence in Haematological Diseases” aims at using European data of patients affected by Sickle Cel...

Background Hepatocellular carcinoma (HCC) is a highly lethal cancer and the second leading cause of cancer-related deaths worldwide. As demonstrated in other solid neoplasms and HCC, infiltrating CD8 ⁺ T cells seem to be related to a better prognosis, but the mechanisms affecting the immune landscape in HCC are still mostly unknown. Necroptosis is...

To evaluate the antisymmetry of the different methods, we used an extended version of Ssym, which includes 10 more variants that we collected from ThemoMutDB, adding 10 new protein structures of the mutants. This file contains all the aggregated predictions on the augmented version of the Ssym dataset. The predictions are calculated using the exper...

From ThermoMutDB, we extracted 900 variants belonging to proteins having less than 25% sequence identity with those of S2648 and VariBench, whose union includes variants from almost all the thermodynamic studies available in the literature. We therefore revised all the papers related to these 900 variants, and we decided to exclude about ∼24% of th...

To evaluate the antisymmetry of the different methods, we used an extended version of Ssym, which includes 10 more variants that we collected from ThemoMutDB, adding 10 new protein structures of the mutants. This file contains all the aggregated predictions on the augmented version of the Ssym dataset. The predictions are calculated using the ROSET...

Clusters based on sequence similarity using blastclust output with a threshold of 25% sequence identity. The file contains the clusters generated by the union of S669, S2648 and VariBench protein sequences. Each protein is also labelled with the name of the original set (S669, S2648 and VariBench). No clusters of S2648 or VariBench contain sequence...

Predicting the difference in thermodynamic stability between protein variants is crucial for protein design and understanding the genotype-phenotype relationships. So far, several computational tools have been created to address this task. Nevertheless, most of them have been trained or optimized on the same and ‘all’ available data, making a fair...

Background: Early diagnosis is the most effective intervention to improve the prognosis of cutaneous melanoma. Even though the introduction of dermoscopy has improved the diagnostic accuracy, it can still be difficult to distinguish some melanomas from benign melanocytic lesions. Digital dermoscopy monitoring can identify dynamic changes of melano...

Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To inve...

Several studies have linked disruptions of protein stability and its normal functions to disease. Therefore, during the last few decades, many tools have been developed to predict the free energy changes upon protein residue variations. Most of these methods require both sequence and structure information to obtain reliable predictions. However, th...

Background & aims Non-Invasive Scoring Systems (NSS) are used to identify NAFLD patients at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extra-hepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain. Methods The most common NSS (N...

Newly differentiated pancreatic β cells lack proper insulin secretion profiles of mature functional β cells. The global gene expression differences between paired immature and mature β cells have been studied, but the dynamics of transcriptional events, correlating with temporal development of glucose-stimulated insulin secretion (GSIS), remain to...

The prediction of free energy changes upon protein residue variations is an important application in biophysics and biomedicine. Several methods have been developed to address this problem so far, including physical-based and machine learning models. However, most of the current computational tools, especially data-driven approaches, fail to incorp...

Conventional/targeted chemotherapies and ionizing radiation (IR) are being used both as monotherapies and in combination for the treatment of epithelial ovarian cancer (EOC). Several studies show that these therapies might favor oncogenic signaling and impede anti-tumor responses. MiR-200c is considered a master regulator of EOC-related oncogenes....

Background Atrial fibrillation (AF) is a well-established post-cardiac surgery complication. Orthotopic heart transplantation (OHT) represents a peculiar condition where surgical thoracic veins isolation and autonomic denervation occur. This study aims at investigating AF incidence in OHT in order to define its risk factors and to evaluate its prog...

Missense variants are among the most studied genome modifications as disease biomarkers. It has been shown that the “perturbation” of the protein stability upon a missense variant (in terms of absolute ΔΔG value, i.e., |ΔΔG|) has a significant, but not predictive, correlation with the pathogenicity of that variant. However, here we show that this c...

Protein stability predictions are becoming essential in medicine to develop novel immunotherapeutic agents and for drug discovery. Despite the large number of computational approaches for predicting the protein stability upon mutation, there are still critical unsolved problems: 1) the limited and unbalanced number of thermodynamic measurements for...

Aim: The novel primary end-point of the present study was to ascertain β-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible ro...

Background Differential diagnosis between malignant pleural mesothelioma (MPM) and benign mesothelial conditions is still challenging and there is a lack of useful markers. Programmed cell death 4 (PDCD4) is a well-known tumor suppressor gene in several cancers, its post-transcriptional activity is directly controlled by miR-21, whose over-expressi...

Islet β cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that β cells of newborns secrete more insulin than adults in response to similar intracellular Ca2+ concentrations, suggesting differences in the Ca2+ sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a...

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing d...

Single-cell diversity in the brain The cells that make up an organism may all start from one genome, but somatic mutations mean that somewhere along the line of development, an organism's individual cellular genomes diverge. McConnell et al. review the implications and causes of single-cell genomic diversity for brain function. Somatic mutations ca...

The Spalt-Like Transcription Factor 4 (SALL4) oncogene plays a central function in embryo-fetal development and is absent in differentiated tissues. Evidence suggests that it can be reactivated in several cancers worsening the prognosis. We aimed at investigating the risk associated with SALL4 reactivation for all-cause mortality and recurrence in...

In this study we focused on determining the transcriptome differences between Waldenström's Macroglobulinemia (WM) and IgM Monoclonal Gammopathy of Undetermined Significance (IgM-MGUS) by gene expression profiling (GEP) considering all the different transcript isoforms of genes that map the human transcriptome (coding transcripts, non-coding transc...

Acute Myeloid Leukemia (AML) is a fatal hematological cancer. The genetic abnormalities underlying AML are extremely heterogeneous among patients, making prognosis and treatment selection very difficult. While clinical proteomics data has the potential to improve prognosis accuracy, thus far, the quantitative means to do so have yet to be developed...

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silic...

Dynamic expression data, nowadays obtained using high-throughput RNA sequencing, are essential to monitor transient gene expression changes and to study the dynamics of their transcriptional activity in the cell or response to stimuli. Several methods for data selection, clustering and functional analysis are available; however, these steps are usu...

Background & AimsMicroRNAs (miRNAs) have been involved in hepatocarcinogenesis, but little is known on their role in the progression of chronic viral hepatitis. Aim of this study was to identify miRNA signatures associated with stages of disease progression in patients with chronic viral hepatitis.Methods MiRNA expression profile was investigated i...

In systems genetics, genetic variations can be thought as a randomized, multifactorial set of perturbations and the gene/protein expression profile of each individual as the system response to a specific set of perturbations. Current systems genetics approaches, known as genetics genomics, try to combine different types of data such as expression a...

Traditional methods for flow cytometry (FCM) data processing rely on subjective manual gating. Recently, several groups have developed computational methods for identifying cell populations in multidimensional FCM data. The Flow Cytometry: Critical Assessment of Population Identification Methods (FlowCAP) challenges were established to compare the...

Background: High-throughput (HT) technologies provide huge amount of gene expression data that can be used to identify biomarkers useful in the clinical practice. The most frequently used approaches first select a set of genes (i.e. gene signature) able to characterize differences between two or more phenotypical conditions, and then provide a fun...

Source code of KDVS. Format: ZIP. It contains the Python source code, the documentation, and the internal data files.

Example script performing microarray data normalization and quality check. Format: R. The proper input directory and chip type must be provided. The script uses aroma folder structure to identify input data.