Kristina Zguro
A5044437430- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Genomics and Rare Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics and Neurodevelopmental Disorders
- Genetic Associations and Epidemiology
- PARP inhibition in cancer therapy
- Respiratory viral infections research
- Inflammasome and immune disorders
- Machine Learning in Bioinformatics
- Cell Adhesion Molecules Research
- Cystic Fibrosis Research Advances
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- Liver Disease Diagnosis and Treatment
- Congenital heart defects research
- interferon and immune responses
- Venous Thromboembolism Diagnosis and Management
- Autism Spectrum Disorder Research
- Immunodeficiency and Autoimmune Disorders
- Platelet Disorders and Treatments
- Genetic Neurodegenerative Diseases
- Genetic Mapping and Diversity in Plants and Animals
- Telomeres, Telomerase, and Senescence
University of Siena
2021-2024
IRCCS Humanitas Research Hospital
2023
Abstract Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across life course; a key benefit over short-term prediction models. To produce estimates relevant clinical and public health decision-making, it is important account varying effects due age sex. Here, we develop novel framework estimate country-, age-, sex-specific of cumulative incidence stratified by PGS 18 high-burden diseases. We integrate associations from seven studies in four countries ( N...
Intellectual disability (ID) is characterized by impairments in the cognitive processes and tasks of daily life. It encompasses a clinically genetically heterogeneous group neurodevelopmental disorders often associated with autism spectrum disorder (ASD). Social communication abilities are strongly compromised ASD. The prevalence ID/ASD 1–3%, approximately 30% patients remain without molecular diagnosis. Considering extreme genetic locus heterogeneity, next-generation sequencing approaches...
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, from whole-exome sequencing data about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting severity. First, converted into separate sets Boolean features, depending on the absence or presence each gene. An ensemble LASSO logistic regression models was identify most informative features with respect genetic...
Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders occur in ~1% of the general population. Due disease heterogeneity, identifying etiology ID ASD remains challenging. Exome sequencing (ES) offers opportunity rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES a cohort 200 patients: 84 isolated 116 ASD. We identified 41 pathogenic detection rate 22% (43/200): 39% patients (33/84) 9% ID/ASD...
The clinical presentation of COVID-19 is extremely heterogeneous, ranging from asymptomatic to severely ill patients. Thus, host genetic factors may be involved in determining disease and progression. Given that carriers single cystic fibrosis (CF)-causing variants the
Extreme polymorphism of HLA and killer‐cell immunoglobulin‐like receptors (KIR) differentiates immune responses across individuals. Additional to T cell receptor interactions, subsets class I act as ligands for inhibitory activating KIR, allowing natural killer (NK) cells detect kill infected cells. We investigated the impact KIR on severity COVID‐19. High resolution II genotypes were determined from 403 non‐hospitalized 1575 hospitalized SARS‐CoV‐2 patients Italy collected in 2020. observed...
Whole exome sequencing has provided significant opportunities to discover novel candidate genes for intellectual disability and autism spectrum disorders. Variants in the spectrin SPTAN1, SPTBN1, SPTBN2 , SPTBN4 have been associated with neurological disorders; however, SPTBN5 gene-variants not any human disorder. This is first report that associates gene variants (ENSG00000137877: c.266A>C; p.His89Pro, c.9784G>A; p.Glu3262Lys, c.933C>G; p.Tyr311Ter, c.8809A>T;...
Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of pathology termed Disease 19 (COVID-19). Several studies reported both COVID-19 and RTEL1 variants are associated with shorter telomere length, but direct association between the two not generally acknowledged. Here we demonstrate up to 8.6% severe patients bear ultra-rare variants, show how this subgroup can be recognized. Methods A cohort 2246...
Abstract Polygenic Scores (PGSs) offer the ability to predict genetic risk for complex disease across life course; a key benefit over short-term prediction models. To produce estimates relevant clinical and public health decision making, it is important account any varying effects due common factors such as age sex. Here, we develop novel framework estimate cumulative incidences course country-, age-, sex-specific of incidence stratified by PGS 18 high-burden diseases integrating...
Host genetics is an emerging theme in COVID-19. A handful of common polymorphisms and some rare variants have been identified, either through GWAS or candidate gene approach, respectively. However, organic model still missing. Here, we propose a that takes into account both coding variants. This has piloted cohort 1,318 Italian SARS-CoV-2 positive individuals. Ordered logistic regression clinical WHO grading on age, stratified by sex, was used to obtain binary phenotypic classification...
Abstract Alport syndrome is a rare genetic kidney disease caused by variants in the COL4A3/A4/A5 genes. It’s characterised progressive failure, though therapies targeting Renin-Angiotensin System can delay its progression. Additionally, extrarenal manifestations may sometimes coexist. Recent advances analysis and necessity to better clarify genotype-phenotype correlations affected patients raises importance of detecting even cryptic splicing variants, lying both canonical non-canonical...
Abstract We employed a multifaceted computational strategy to identify the genetic factors contributing increased risk of severe COVID-19 infection from Whole Exome Sequencing (WES) dataset cohort 2000 Italian patients. coupled stratified k -fold screening, rank variants more associated with severity, training multiple supervised classifiers, predict severity based on screened features. Feature importance analysis tree-based models allowed us 16 highest support which, together age and gender...
Carriers of single pathogenic variants the
Abstract Understanding disease progression is of a high biological and clinical interest. Unlike susceptibility whose genetic basis has been abundantly studied, less known about the genetics its overlap with susceptibility. Considering ten common diseases (N cases ranging from 17,152 to 99,666) across seven biobanks, we systematically compared architecture progression, defined as disease-specific mortality. We identified only one locus significantly associated mortality show that, at similar...
Abstract Host genetics is an emerging theme in COVID-19 and few common polymorphisms some rare variants have been identified, either by GWAS or candidate gene approach, respectively. However, organic model still missing. Here, we propose a new that takes into account germline applied cohort of 1,300 Italian SARS-CoV-2 positive individuals. Ordered logistic regression clinical WHO grading on sex age was used to obtain binary phenotypic classification. Genetic variability from WES synthesized...
Abstract Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology this phenomenon not well understood. A cohort 1,186 subjects, from GEN-COVID consortium, infected by SARS-CoV-2 with different were stratified sex adjusted age. Then, common coding variants whole exome sequencing mined LASSO logistic regression. The homozygosity cell adhesion molecule P-selectin gene ( SELP) rs6127 (c.1807G>A; p.Asp603Asn) which increases platelet activation found to...
Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura severe autosomal recessive disorder characterized by uncleaved ultra-large vWF thrombotic microangiopathy, frequently triggered infections. Carriers to be asymptomatic. Exome analysis about 3000 SARS-CoV-2 infected subjects different severities, belonging the GEN-COVID cohort, revealed...
Abstract The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, from whole exome sequencing data about 4,000 SARS-CoV-2-positive individuals were used to define an interpretable machine learning model for predicting severity. Firstly, converted into separate sets Boolean features, depending on the absence or presence each gene. An ensemble LASSO logistic regression models was identify most informative features with...
Almost half of all individuals affected by intellectual disability (ID) remain undiagnosed. In the Solve-RD project, exome sequencing (ES) datasets from unresolved with (syndromic) ID (n = 1,472 probands) are systematically reanalyzed, starting raw files, followed genome-wide variant calling and new data interpretation. This strategy led to identification a disease-causing de novo missense in TUBB3 girl severe developmental delay, secondary microcephaly, brain imaging abnormalities, high...