Maria Persico | TIGEM - Academia.edu (original) (raw)

Papers by Maria Persico

Environmental Pollution, 2021

Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to path... more Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to pathophysiological changes in the gastrointestinal system. The organochlorine pesticide dieldrin is a persistent environmental contaminant that bioaccumulates in fatty tissue of aquatic organisms. The objectives of this study were to determine whether environmentally-relevant doses of dieldrin altered gastrointestinal morphology and the microbiome of zebrafish. Adult zebrafish at ∼4 months of age were fed a measured amount of feed containing either a solvent control or one of two doses of dieldrin (measured at 16, and 163.5 ng/g dry weight) for 4 months. Dieldrin body burden levels in zebrafish after four-month exposure were 0 (control), 11.47 ± 1.13 ng/g (low dose) and 18.32 ± 1.32 ng/g (high dose) wet weight [mean ± std]. Extensive histopathology at the whole organism level revealed that dieldrin exposure did not induce notable tissue pathology, including the gastrointestinal tract. A repeated measure mixed model analysis revealed that, while fish gained weight over time, there were no dieldrin-specific effects on body weight. Fecal content was collected from the gastrointestinal tract of males and 16S rRNA gene sequencing conducted. Dieldrin at a measured feed dose of 16 ng/g reduced the abundance of Firmicutes, a phylum involved in energy resorption. At the level of class, there was a decrease in abundance of Clostridia and Betaproteobacteria, and an increase in Verrucomicrobiae species. We used a computational approach called predicted relative metabolomic turnover (PRMT) to predict how a shift in microbial community composition affects exchange of metabolites. Dieldrin was predicted to affect metabolic turnover of uroporphyrinogen I and coproporphyrinogen I [enzyme]-cysteine, hydrogen selenide, selenite, and methyl-selenic acid in the fish gastrointestinal system. These pathways are related to bacterial heme biosynthesis and selenium metabolism. Our study demonstrates that dietary exposures to dieldrin can alter microbiota composition over 4 months, however the long-term consequences of such impacts are not well understood.

<b>Copyright information:</b>Taken from "HomoMINT: an inferred human network bas... more <b>Copyright information:</b>Taken from "HomoMINT: an inferred human network based on orthology mapping of protein interactions discovered in model organisms"BMC Bioinformatics 2005;6(Suppl 4):S21-S21.Published online 1 Dec 2005PMCID:PMC1866386. out in the protein table by entering in the form one of the following: a protein name, a Uniprot or a PDB identifier, a keyword, an InterPro domain or a gene ontology term (top part of the form). Alternatively the search can be carried out on the interaction table (centre). Finally (lower part) a BLAST search can be carried out by entering a protein sequence. B) Search output listing on the right the partners of the query protein and on the left the experimental evidence supporting the interactions. C) The Mint Viewer is an applet that permits the graphic display of interaction networks. Edges marked by small blue circles indicate that the corresponding interactions were inferred from experiments carried out in model organisms, while yellow circles mark interactions supported by direct experimental results. Interactions that are inferred from model organisms but are also supported by direct experiments are marked by yellow circles with a blue contour. A series of check boxes make it possible to visualize interactions inferred by any combination of model organism interactomes.

Investigative Ophthalmology & Visual Science, 2016

Environmental Pollution, 2021

Nature Immunology, 2001

Dendritic cells (DCs) are strong activators of primary T cell responses. Their priming ability is... more Dendritic cells (DCs) are strong activators of primary T cell responses. Their priming ability is acquired upon encounter with maturation stimuli. To identify the genes that are differentially expressed upon maturation induced by exposure to Gram-negative bacteria, a kinetic study of DC gene expression was done with microarrays representing 11,000 genes and ESTs (expressed sequence tags). Approximately 3000 differentially expressed transcripts were identified. We found that functional interleukin 2 (IL-2) mRNA, which gave rise to IL-2 production, was transiently up-regulated at early time-points after bacterial encounter. In contrast, macrophages did not produce IL-2 upon bacterial stimulation. Thus, IL-2 is an additional key cytokine that confers unique T cell stimulatory capacity to DCs.

Scientific reports, Jan 23, 2018

In longitudinal clinical studies, methodologies available for the analysis of multivariate data w... more In longitudinal clinical studies, methodologies available for the analysis of multivariate data with multivariate methods are relatively limited. Here, we present Consensus Clustering (CClust) a new computational method based on clustering of time profiles and posterior identification of correlation between clusters and predictors. Subjects are first clustered in groups according to a response variable temporal profile, using a robust consensus-based strategy. To discover which of the remaining variables are associated with the resulting groups, a non-parametric hypothesis test is performed between groups at every time point, and then the results are aggregated according to the Fisher method. Our approach is tested through its application to the EarlyBird cohort database, which contains temporal variations of clinical, metabolic, and anthropometric profiles in a population of 150 children followed-up annually from age 5 to age 16. Our results show that our consensus-based method is ...

Nucleic Acids Research, 2016

MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNom... more MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina.

Current Bioinformatics

http://benthamscience.com/contents.php?in=111127&m=July&y=2013 A number of representations of pro... more http://benthamscience.com/contents.php?in=111127&m=July&y=2013 A number of representations of protein networks have been reported. Further, while the existence of multiple types of interactomes and relationships between proteins has been accepted and discussed extensively, the exploration of these concepts and hypotheses using machine learning frameworks for protein interaction prediction in a multi-class setting has not yet been extensively accomplished. Essentially, this is due to two reasons: the missing values issues in features and the heterogeneity and not always clear annotation of protein interaction data. This has motivated the attempt to build a set of universal features attributable to any set of protein pairs, generating an universal feature space where evolutionary constraints show their effects and play a central role. We have called this space and the features generating it respectively the sequence properties space and the derived features. We have probed an integrat...

Current Bioinformatics, 2013

A number of representations of protein networks have been reported. Further, while the existence ... more A number of representations of protein networks have been reported. Further, while the existence of multiple types of interactomes and relationships between proteins has been accepted and discussed extensively, the exploration of these concepts and hypothesis using machine learning frameworks for protein interaction prediction in a multi-class setting has not yet been extensively accomplished. This is essentially due to two reasons: the missing values issues in features and the heterogeneity and not always clear annotation of protein interaction data. This has motivated the attempt to build a set of universal features attributable to any set of protein pairs, generating an universal feature space where evolutionary constraints show their effects and play a central role. We have called this space and the features generating it respectively the sequence properties space and the derived features. We have probed an integrated version of sequence properties space in its ability to properly represent the different kind of available interactomes.

eLife, 2015

Cystic fibrosis (CF) is caused by mutations in CF transmembrane conductance regulator (CFTR). The... more Cystic fibrosis (CF) is caused by mutations in CF transmembrane conductance regulator (CFTR). The most frequent mutation (F508del-CFTR) results in altered proteostasis, i.e., in the misfolding and intracellular degradation of the protein. The F508del-CFTR proteostasis machinery and its homeostatic regulation are well studied, while the question whether &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;classical&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; signalling pathways and phosphorylation cascades might control proteostasis remains barely explored. Here, we have unravelled signalling cascades acting selectively on the F508del-CFTR folding-trafficking defects by analysing the mechanisms of action of F508del-CFTR proteostasis regulator drugs through an approach based on transcriptional profiling followed by deconvolution of their gene signatures. Targeting multiple components of these signalling pathways resulted in potent and specific correction of F508del-CFTR proteostasis and in synergy with pharmacochaperones. These results provide new insights into the physiology of cellular proteostasis and a rational basis for developing effective pharmacological correctors of the F508del-CFTR defect.

eLife, 2015

Tissue specificity where cells perform drastically different functions despite having identical D... more Tissue specificity where cells perform drastically different functions despite having identical DNA requires many complex mechanisms to control gene expression. Tissue specificity is also an important aspect of many genetic diseases, reflect ing the potentially different roles of proteins and pathways in diverse cell lineages. Tissue-specific mechanisms of control may be captured in co- expression networks,where two genes are connected in the network if their expression levels are correlated .Integrated networks where information on physical interactions between proteins has been filtered on the basis of coexpression levels have been proposed. The recent publication of a first human proteome draft from two different groups ([1][2]), gives raise the possibility to extend previously elaborated methods to the fiel d of quantitative proteomics. We propose a pilot strategy to model tissue - specific functional networks centered around some exemplar disease genes. We have used integrated ...

Developmental Cell, 2014

A fundamental property of cellular processes is to maintain homeostasis despite varying internal ... more A fundamental property of cellular processes is to maintain homeostasis despite varying internal and external conditions. Within the membrane transport apparatus, variations in membrane fluxes from the endoplasmic reticulum (ER) to the Golgi complex are balanced by opposite fluxes from the Golgi to the ER to maintain homeostasis between the two organelles. Here we describe a molecular device that balances transport fluxes by integrating transduction cascades with the transport machinery. Specifically, ER-to-Golgi transport activates the KDEL receptor at the Golgi, which triggers a cascade that involves Gs and adenylyl cyclase and phosphodiesterase isoforms and then PKA activation and results in the phosphorylation of transport machinery proteins. This induces retrograde traffic to the ER and balances transport fluxes between the ER and Golgi. Moreover, the KDEL receptor activates CREB1 and other transcription factors that upregulate transport-related genes. Thus, a Golgi-based control system maintains transport homeostasis through both signaling and transcriptional networks.

Proceedings of the First ACM International Conference on Bioinformatics and Computational Biology - BCB '10, 2010

Classification of proteins as Interacting - Non Interacting is a machine learning problem carried... more Classification of proteins as Interacting - Non Interacting is a machine learning problem carried out either with informative or with discriminative approaches by many researchers [21, 27, 9]. Missing information about the features describing the two classes is one of the main problems to deal with, and alternative models were proposed as possibly more effective solutions [12]. As a matter of fact, at the top positions in the list of desiderata for features aimed to Learning Interacting Class there are: the universality (high coverage) and the discrimination power or class specificity. Here, the problem related to missing information in the features is bypassed by adapting single protein properties of universal coverage (i.e. available for all the yeast proteome) to become protein pairs attributes, still of universal coverage; the encoding information strategy is based on exploiting the apparent combinatorial nature of the association between single protein features to the classes of Interacting - Non Interacting protein pairs.

Biochimica et biophysica acta, Jan 12, 2014

More than twenty different genetic diseases have been described that are caused by mutations in p... more More than twenty different genetic diseases have been described that are caused by mutations in phosphoinositide metabolizing enzymes, mostly in phosphoinositide phosphatases. Although generally ubiquitously expressed, mutations in these enzymes, which are mainly loss-of-function, result in tissue-restricted clinical manifestations through mechanisms that are not completely understood. Here we analyze selected disorders of phosphoinositide metabolism grouped according to the principle tissue affected: the nervous system, muscle, kidney, the osteoskeletal system, the eye, and the immune system. We will highlight what has been learnt so far from the study of these disorders about not only the cellular and molecular pathways that are involved or are governed by phosphoinositides, but also the many gaps that remain to be filled to gain a full understanding of the pathophysiological mechanisms underlying the clinical manifestations of this steadily growing class of diseases, most of whic...

FEBS Letters, 2005

The behavior, morphology and response to stimuli in biological systems are dictated by the intera... more The behavior, morphology and response to stimuli in biological systems are dictated by the interactions between their components. These interactions, as we observe them now, are therefore shaped by genetic variations and selective pressure. Similar to what has been achieved by comparing genome structures and protein sequences, we hope to obtain valuable information about systemsÕ evolution by comparing the organization of interaction networks and by analyzing their variation and conservation. Equally, significantly we can learn whether and how to extend the network information obtained experimentally in well-characterized model systems to different organisms. We conclude from our analysis that, despite the recent completion of several high throughput experiments aimed at the description of complete interactomes, the available interaction information is not yet of sufficient coverage and quality to draw any biologically meaningful conclusion from the comparison of different interactomes. Thus, the transfer of network information obtained from simple organism to evolutionary distant species should be carried out and considered with caution. By using smaller higher-confidence datasets, a larger fraction of interactions is shown to be conserved; this suggests that with the development of more accurate experimental and informatic approaches, we will soon be in the position to study the network evolution.

Their priming ability is acquired upon encounter with maturation stimuli. To identify the genes t... more Their priming ability is acquired upon encounter with maturation stimuli. To identify the genes that are differentially expressed upon maturation induced by exposure to Gram-negative bacteria, a kinetic study of DC gene expression was done with microarrays representing 11,000 genes and ESTs (expressed sequence tags). Approximately 3000 differentially expressed transcripts were identified. We found that functional interleukin 2 (IL-2) mRNA, which gave rise to IL-2 production, was transiently upregulated at early time-points after bacterial encounter. In contrast, macrophages did not produce IL-2 upon bacterial stimulation. Thus, IL-2 is an additional key cytokine that confers unique T cell stimulatory capacity to DCs.

Environmental Pollution, 2021

Investigative Ophthalmology & Visual Science, 2016

Environmental Pollution, 2021

Nature Immunology, 2001

Scientific reports, Jan 23, 2018

Nucleic Acids Research, 2016

Current Bioinformatics

Current Bioinformatics, 2013

eLife, 2015

Developmental Cell, 2014

Proceedings of the First ACM International Conference on Bioinformatics and Computational Biology - BCB '10, 2010

Biochimica et biophysica acta, Jan 12, 2014

FEBS Letters, 2005