Alfredo Pulvirenti

University of Catania | UNICT · Department of Mathematics and Computer Science (DMI)

Consider a large labeled graph (network), denoted the target. Subgraph matching is the problem of finding all instances of a small subgraph, denoted the query, in the target graph. Unlike the majority of existing methods that are restricted to graphs with labels solely on vertices, our proposed approach, named can effectively handle graphs with lab...

A new chemiluminescence immunoassay method (CLIA) for detecting IgA anti-transglutaminase (atTG IgA) in celiac disease (CD) has prompted inquiries into its diagnostic performance. We conducted a systematic review and meta-analysis comparing CLIA with traditional enzyme-linked immunosorbent assay (ELISA) and fluorescence enzyme immunoassay (FEIA). W...

Motivation The rapid increase of bio-medical literature makes it harder and harder for scientists to keep pace with the discoveries on which they build their studies. Therefore, computational tools have become more widespread, among which network analysis plays a crucial role in several life-science contexts. Nevertheless, building correct and comp...

Multi-layer Complex networks are commonly used for modeling and analysing biological entities. This paper presents the advantage of using COMBO (Combining Multi Bio Omics) to suggest a new role of the chromosomal aberration as a cancer driver factor. Exploiting the heterogeneous multi-layer networks, COMBO integrates gene expression and DNA-methyla...

Background In the precision medicine era, identifying predictive factors to select patients most likely to benefit from treatment with immunological agents is a crucial and open challenge in oncology. Methods This paper presents a pan-cancer analysis of Tumor Mutational Burden (TMB). We developed a novel computational pipeline, TMBcalc, to calcula...

Network motifs are subgraphs of a network that occur more frequently than expected, according to some reasonable null model. They represent building blocks of complex systems such as genetic interaction networks or social networks and may reveal intriguing typical but perhaps unexpected relationships between interacting entities. The identification...

tRNA-derived ncRNAs are a heterogeneous class of non-coding RNAs recently proposed to be active regulators of gene expression and be involved in many diseases, including cancer. Consequently, several online resources on tRNA-derived ncRNAs have been released. Although interesting, such resources present only basic features and do not adequately exp...

Chronic lymphocytic leukemia (CLL) is one of the most diagnosed forms of leukemia worldwide and it is usually classified into two forms: indolent and aggressive. These two forms are characterized by distinct molecular features that drive different responses to treatment and clinical outcomes. In this context, a better understanding of the molecular...

Objective: Next Generation Sequencing (NGS) has evolved into a mature technology that is becoming increasingly prevalent in the clinical setting. However, one of the significant challenges physicians and oncologists face is effectively handling the vast amount of genome-scale data generated by NGS experiments and translating it into actionable insi...

The discovery of differential gene-gene correlations across phenotypical groups can help identify the activation/deactivation of critical biological processes underlying specific conditions. The presented R package, provided with a count and design matrix, extract networks of group-specific interactions that can be interactively explored through a...

The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially wit...

Multi-layer Complex networks are commonly used for modeling and analysing biological entities. This paper presents a new computational framework called COMBO (Combining Multi Bio Omics) for generating and analyzing heterogeneous multi-layer networks. Our model uses gene expression and DNA-methylation data. The power of COMBO relies on its ability t...

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide. Among its subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the most common, accounting for more than 85% of lung cancer diagnoses. Despite the incredible efforts and recent advances in lung cancer treatments, pa...

Background To determine whether gene-gene interaction network analysis of RNA sequencing (RNA-Seq) of synovial biopsies in early rheumatoid arthritis (RA) can inform our understanding of RA pathogenesis and yield improved treatment response prediction models. Methods We utilized four well curated pathway repositories obtaining 10,537 experimentall...

Motivation The study of the Human Virome remains challenging nowadays. Viral metagenomics, through high-throughput sequencing data, is the best choice for virus discovery. The metagenomics approach is culture-independent and sequence-independent, helping search for either known or novel viruses. Though it is estimated that more than 40% of the viru...

Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issu...

The PHENotype SIMulator, is a systems biology tool, which leverages available transcriptomic and proteomic databases to model of SARS-CoV-2 host-infection in silico. PHENSIM can determine the viral effects on cellular host-immune responses, which we recently applied to in silico drug repurposing for COVID-19. There is a clear importance of previous...

The inference of novel knowledge and new hypotheses from the current literature analysis is crucial in making new scientific discoveries. In bio-medicine, given the enormous amount of literature and knowledge bases available, the automatic gain of knowledge concerning relationships among biological elements, in the form of semantically related term...

A broad ecosystem of resources, databases, and systems to analyze cancer variations is present in the literature. These are a strategic element in the interpretation of NGS experiments. However, the intrinsic wealth of data from RNA-seq, ChipSeq, and DNA-seq can be fully exploited only with the proper skill and knowledge. In this chapter, we survey...

The wealth of knowledge and multi-omics data available in drug research has allowed the rise of several computational methods in the drug discovery field, resulting in a novel and exciting strategy called drug repurposing. Drug repurposing consists in finding new applications for existing drugs. Numerous computational methods perform a high-level i...

With the advent of OMICs technologies, several bioinformatics methods have been developed to infer biological knowledge from such data. Pathway analysis methodologies help integrate multi-OMICs data and find altered function in known metabolic and signaling pathways. As widely known, such alterations promote the cancer cells' progression and the ma...

Background The rapidly increasing biological literature is a key resource to automatically extract and gain knowledge concerning biological elements and their relations. Knowledge Networks are helpful tools in the context of biological knowledge discovery and modeling. Results We introduce a novel system called NETME, which, starting from a set of...

The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG...

The present study aimed to investigate the personal well-being and family distress of Italian caregivers during the lockdown. Five hundred sixty-five family caregivers and 638 age-and sex-matched noncaregivers completed a web-based survey. The following scales were administered to all participants: General Health Questionnaire-12 items (GHQ-12), In...

The study of gene-gene interactions in RNA-Sequencing (RNA-Seq) data has traditionally been hard owing the large number of genes detectable by Next-Generation Sequencing (NGS). However, differential gene-gene pairs can inform our understanding of biological processes and yield improved prediction models. Here, we utilised four well curated pathway...

The insulin receptor isoform A (IR-A) plays an increasingly recognized role in fetal growth and tumor biology in response to circulating insulin and/or locally produced IGF2. This role seems not to be shared by the IR isoform B (IR-B). We aimed to dissect the specific impact of IR isoforms in modulating insulin signaling in triple negative breast c...

Temporal networks are graphs where each edge is associated with a timestamp denoting when two nodes interact. Temporal Subgraph Isomorphism (TSI) aims at retrieving all the subgraphs of a temporal network (called target) matching a smaller temporal network (called query), such that matched target edges appear in the same chronological order of corr...

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and, although its genetic background has been extensively studied, little is known about the contribution of non-coding RNAs (ncRNAs) to its pathogenesis. Indeed, its competitive endogenous RNA (ceRNA) regulatory network comprising microRNAs (miRNAs), long non-codi...

Despite the unprecedented growth in our understanding of cell biology, it still remains challenging to connect it to experimental data obtained with cells and tissues’ physiopathological status under precise circumstances. This knowledge gap often results in difficulties in designing validation experiments, which are usually labor-intensive, expens...

Background RNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this technology produces a vast amount of data requiring sophisticated computational approaches for their analysis than other traditional technologies such as Real-Time PCR or micro...

The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with very few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especiall...

The huge amount of biological literature, which daily increases, represents a strategic resource to automatically extract and gain knowledge concerning relations among biological elements. Knowledge Networks are helpful tools in the context of biological knowledge discovery and modeling. Here we introduce a novel system called NETME, which, startin...

Temporal networks are graphs where each edge is associated with a timestamp or an interval indicating when an interaction between two nodes happens. The Temporal Subgraph Isomorphism (TSI) problem aims at identifying all the subgraphs of a temporal network (called target) matching a smaller temporal network (called query), such that matched target...

Purpose To conduct a systematic review with network meta‐analysis (NMA) of randomized clinical trials (RCTs) comparing panretinal photocoagulation (PRP) versus anti‐vascular endothelial growth factor (VEGF) treatment alone or in combination with PRP, for proliferative diabetic retinopathy (PDR). Methods PubMed, Medline and Embase databases were se...

p>Purpose: To compare efficacy of treat and extend (T&E) versus fixed regimen treatment protocols in neovascular age-related macular degeneration (nAMD). Methods: Randomized clinical trials (RCTs) comparing T&E versus fixed regimen protocols for nAMD were systematically searched. Primary outcome was to compare the mean best corrected visual acuity...

Complex networks are usually characterized by the presence of small and recurrent patterns of interactions between nodes, called network motifs. These small modules can help to elucidate the structure and the functioning of complex systems. Assessing the statistical significance of a pattern as a motif in a network G is a time consuming task which...

Gilles de la Tourette syndrome (GTS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with male predominance, frequently comorbid, that share clinical and behavioral features. The incidence of ASD in patients affected by GTS was reported to be between 2.9% and 22.8%. We hypothesized that higher ASD rates among children affect...

Background We use a new pathway analysis tool MITHrIL (Mirna enriched paTHway Impact anaLysis) to analyse RNA-seq patterns in synovial biopsies from patients with rheumatoid arthritis from the Pathobiology of Early Arthritis Cohort (PEAC). MITHrIL augments pathways with missing regulatory elements, such as microRNAs, and their interactions with gen...

The Subgraph Matching (SM) problem consists of finding all the embeddings of a given small graph, called the query, into a large graph, called the target. The SM problem has been widely studied for simple graphs, i.e. graphs where there is exactly one edge between two nodes and nodes have single labels, but few approaches have been devised for labe...

Despite the unprecedented growth in our understanding of cell biology, it still remains challenging to connect it to experimental data obtained with cells and tissues’ physiopathological status under precise circumstances. This knowledge gap often results in difficulties in designing validation experiments, which are usually labor-intensive, expens...

Network motifs have a central role in explaining the functionality of complex systems. Establishing motif significance requires the computation of the expected number of their occurrences according to a random graph model. Few models have been proposed to analytically derive the expected number of non-induced occurrences of a motif. In this paper w...

Background: Several large public repositories of microarray datasets and RNA-seq data are available. Two prominent examples include ArrayExpress and NCBI GEO. Unfortunately, there is no easy way to import and manipulate data from such resources, because the data is stored in large files, requiring large bandwidth to download and special purpose da...

Importance Although intravitreal anti–vascular endothelial growth factor (VEGF) treatment represents the first-line therapy for many retinal diseases, the issue of their systemic safety is debatable. Objectives To assess whether intravitreal anti-VEGF therapy might be associated with increased risk of mortality and which variables are associated w...

Next-Generation Sequencing (NGS) is a high-throughput technology widely applied to genome sequencing and transcriptome profiling. RNA-Seq uses NGS to reveal RNA identities and quantities in a given sample. However, it produces a huge amount of raw data that need to be preprocessed with fast and effective computational methods. RNA-Seq can look at d...

Objective: To estimate the incidence of acute cerebral ischaemia detected by magnetic resonance imaging (MRI) in acute central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) and transient monocular vision loss (TMVL). Methods: Studies reporting the incidence of acute cerebral ischaemia, detected by MRI, within 7 days fro...

Pathway analysis is a wide class of methods allowing to determine the alteration of functional processes in complex diseases. However, biological pathways are still partial, and knowledge coming from posttranscriptional regulators has started to be considered in a systematic way only recently. Here we will give a global and updated view of the main...

A labelled multi-relational network (or labelled multigraph, for short) is one in which nodes have labels and a pair of nodes may be connected by an edge with one or more labels. For example, in an airline route database, ‘large European city’ may be the label on the Paris node and ‘large Asian city’ may be the label on the New Delhi node and the e...

Many scientific applications entail solving the subgraph isomorphism problem, i.e., given an input pattern graph, find all the subgraphs of a (usually much larger) target graph that are structurally equivalent to that input. Because subgraph isomorphism is NP-complete, methods to solve it have to use heuristics. This work evaluates subgraph isomorp...

Background: The long-term outcome of potential celiac disease (CD) is still a debated issue. We aimed to evaluate the progression of potential CD versus overt CD after 10-years of follow-up in a cohort of children genetically predisposed to CD. Methods: The CELIPREV study is prospectively following from birth 553 children with CD-predisposing HL...

A wide range of biomedical applications entails solving the subgraph isomorphism problem, i.e. finding all the possible subgraphs of a target graph that are structurally equivalent to an input pattern graph. Targets may be very large and complex structures compared to patterns. Methods that address this NP-complete problem use heuristics. Their per...

The wealth of knowledge and omic data available in drug research allowed the rising of several computational methods in drug discovery field yielding a novel and exciting application called drug repositioning. Several computational methods try to make a high-level integration of all the knowledge in order to discover unknown mechanisms. In this cha...

Next-generation sequencing is increasing our understanding and knowledge of non-coding RNAs (ncRNAs), elucidating their roles in molecular mechanisms and processes such as cell growth and development. Within such a class, tRNA-derived ncRNAs have been recently associated with gene expression regulation in cancer progression. In this paper, we chara...

Autism spectrum disorder (ASD) is currently diagnosed according to behavioral criteria. Biomarkers that identify children with ASD could lead to more accurate and early diagnosis. ASD is a complex disorder with multifactorial and heterogeneous etiology supporting recognition of biomarkers that identify patient subsets. We investigated an easily tes...

Background Internal limiting membrane (ILM) peeling during primary vitrectomy for rhegmatogenous retinal detachment (RRD) prevents the formation of postoperative macular epiretinal membrane (ERM). However, studies that compared vitrectomy with and without ILM peeling for RRD, have reported controversial outcomes. Objective To assess the efficacy o...

Quality assessment by using Newcastle-Ottawa scale. (DOCX)

Funnel plot for the rate of RD recurrence. (TIF)

PRISMA checklist 2009. (DOCX)

Funnel plot for mean BCVA change. (TIF)

Funnel plot for the rate of ERM development. (TIF)

Background: The analysis of tissue-specific protein interaction networks and their functional enrichment in pathological and normal tissues provides insights on the etiology of diseases. The Pan-cancer proteomic project, in The Cancer Genome Atlas, collects protein expressions in human cancers and it is a reference resource for the functional stud...

Over the years, computation has become a fundamental part of the scientific practice in several research fields that goes far beyond the boundaries of natural sciences. Data mining, machine learning, simulations and other computational methods lie today at the hearth of the scientific endeavour in a growing number of social research areas from anth...

Network motif discovery is the problem of finding subgraphs of a network that occur more frequently than expected, according to some reasonable null hypothesis. Such subgraphs may indicate small scale interaction features in genomic interaction networks or intriguing relationships involving actors or a relationship among airlines. When nodes are la...

Growing grapevine (Vitis vinifera) is a key contribution to the economy of many countries. Tools provided by genomics and bioinformatics did help researchers in obtaining biological knowledge about the different cultivars. Several genetic markers for common diseases were identified. Recently, the impact of microbiome has been proved to be of fundam...

Motif discovery is the problem of finding subgraphs of a network that appear surprisingly often. Each such subgraph may indicate a small-scale interaction feature in applications ranging from a genomic interaction network, a significant relationship involving rock musicians, or any other application that can be represented as a network. We look at...