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To date there are several studies focusing on the importance of gut microbiome for human health, however the selection of a universal sampling matrix representative of the microbial biodiversity associated to the gastrointestinal (GI) tract, still represents a challenge. Here we present a study in which, through a deep metabarcoding analysis of the 16S rRNA gene, we compared two sampling matrices, feces (F) and colonic lavage liquid (LL), in order to evaluate their accuracy to represent the complexity of the human gut microbiome. A training set of 37 volunteers was attained and paired F and LL samples were collected from each subject. A preliminary absolute quantification of total 16S rDNA, performed by droplet digital PCR (ddPCR), confirmed that sequencing and taxonomic analysis were performed on same total bacterial abundance obtained from the two sampling methods. The taxonomic analysis of paired samples revealed that, although specific taxa were predominantly or exclusively observed in LL samples, as well as other taxa were detectable only or were predominant in stool, the microbiomes of the paired samples F and LL in the same subject hold overlapping taxonomic composition. Moreover, LL samples revealed a higher biodiversity than stool at all taxonomic ranks, as demonstrated by the Shannon Index and the Inverse Simpson's Index. We also found greater inter-individual variability than intra-individual variability in both sample matrices. Finally, functional differences were unveiled in the gut microbiome detected in the F and LL samples. A significant overrepresentation of 22 and 13 metabolic pathways, mainly occurring in Firmicutes and Proteobacteria, was observed in gut microbiota detected in feces and LL samples, respectively. This suggests that LL samples may allow for the detection of microbes adhering to the intestinal mucosal surface as members of the resident flora that are not easily detectable in stool, most likely representative of a diet-influenced transient microbiota. This first comparative study on feces and LL samples for the study of the human gut microbiome demonstrates that the use of both types of sample matrices may represent a possible choice to obtain a more complete view of the human gut microbiota in response to different biological and clinical questions.
Elisabetta Piancone; Bruno Fosso; Mariangela De Robertis; Elisabetta Notario; Annarita Oranger; Caterina Manzari; Marinella Marzano; Silvia Bruno; Anna Maria D'Erchia; Dominga Maio; Martina Minelli; Ilaria Vergallo; Mauro Minelli; Graziano Pesole. Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome. 2021, 1 .
AMA StyleElisabetta Piancone, Bruno Fosso, Mariangela De Robertis, Elisabetta Notario, Annarita Oranger, Caterina Manzari, Marinella Marzano, Silvia Bruno, Anna Maria D'Erchia, Dominga Maio, Martina Minelli, Ilaria Vergallo, Mauro Minelli, Graziano Pesole. Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome. . 2021; ():1.
Chicago/Turabian StyleElisabetta Piancone; Bruno Fosso; Mariangela De Robertis; Elisabetta Notario; Annarita Oranger; Caterina Manzari; Marinella Marzano; Silvia Bruno; Anna Maria D'Erchia; Dominga Maio; Martina Minelli; Ilaria Vergallo; Mauro Minelli; Graziano Pesole. 2021. "Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome." , no. : 1.
Accurate and timely monitoring of emerging genomic diversity is crucial for limiting the spread of potentially more transmissible/pathogenic strains of SARS-CoV-2. At the time of writing, over 1.8M distinct viral genome sequences have been made publicly available, and a sophisticated nomenclature system based on phylogenetic evidence and expert manual curation has allowed the relatively rapid classification of emerging lineages of potential concern. Here, we propose a complementary approach that integrates fine-grained spatiotemporal estimates of allele frequency with unsupervised clustering of viral haplotypes, and demonstrate that multiple highly frequent genetic variants, arising within large and/or rapidly expanding SARS-CoV-2 lineages, have highly biased geographic distributions and are not adequately captured by current SARS-CoV-2 nomenclature standards. Our results advocate a partial revision of current methods used to track SARS-CoV-2 genomic diversity and highlight the importance of the application of strategies based on the systematic analysis and integration of regional data. Here we provide a complementary, completely automated and reproducible framework for the mapping of genetic diversity in time and across different geographic regions, and for the prioritization of virus variants of potential concern. We believe that the approach outlined in this study will contribute to relevant advances to current genomic surveillance methods.
Matteo Chiara; David Stephen Horner; Erika Ferrandi; Carmela Gissi; Graziano Pesole. Unsupervised classification of SARS-CoV-2 genomic sequences uncovers hidden genetic diversity and suggests an efficient strategy for genomic surveillance. 2021, 1 .
AMA StyleMatteo Chiara, David Stephen Horner, Erika Ferrandi, Carmela Gissi, Graziano Pesole. Unsupervised classification of SARS-CoV-2 genomic sequences uncovers hidden genetic diversity and suggests an efficient strategy for genomic surveillance. . 2021; ():1.
Chicago/Turabian StyleMatteo Chiara; David Stephen Horner; Erika Ferrandi; Carmela Gissi; Graziano Pesole. 2021. "Unsupervised classification of SARS-CoV-2 genomic sequences uncovers hidden genetic diversity and suggests an efficient strategy for genomic surveillance." , no. : 1.
Gene therapy has become an important approach for treating cancer, and electroporation represents a technology for introducing therapeutic genes into a cell. An example of cancer gene therapy relying on gene electrotransfer is the use of immunomodulatory cytokines, such as interleukin 2 (IL-2) and 12 (IL-12), which directly stimulate immune cells at the tumour site. The aim of our study was to determine the effects of gene electrotransfer with two plasmids encoding IL-2 and IL-12 in vitro and in vivo. Two different pulse protocols, known as EP1 (600 V/cm, 5 ms, 1 Hz, 8 pulses) and EP2 (1300 V/cm, 100 µs, 1 Hz, 8 pulses), were assessed in vitro for application in subsequent in vivo experiments. In the in vivo experiment, gene electrotransfer of pIL-2 and pIL-12 using the EP1 protocol was performed in B16.F10 murine melanoma. Combined treatment of tumours using pIL2 and pIL12 induced significant tumour growth delay and 71% complete tumour regression. Furthermore, in tumours coexpressing IL-2 and IL-12, increased accumulation of dendritic cells and M1 macrophages was obtained along with the activation of proinflammatory signals, resulting in CD4+ and CD8+ T-lymphocyte recruitment and immune memory development in the mice. In conclusion, we demonstrated high antitumour efficacy of combined IL-2 and IL-12 gene electrotransfer protocols in low-immunogenicity murine B16.F10 melanoma.
T. Komel; M. Bosnjak; S. Kranjc Brezar; M. De Robertis; M. Mastrodonato; G. Scillitani; G. Pesole; E. Signori; G. Sersa; M. Cemazar. Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma. Bioelectrochemistry 2021, 141, 107843 .
AMA StyleT. Komel, M. Bosnjak, S. Kranjc Brezar, M. De Robertis, M. Mastrodonato, G. Scillitani, G. Pesole, E. Signori, G. Sersa, M. Cemazar. Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma. Bioelectrochemistry. 2021; 141 ():107843.
Chicago/Turabian StyleT. Komel; M. Bosnjak; S. Kranjc Brezar; M. De Robertis; M. Mastrodonato; G. Scillitani; G. Pesole; E. Signori; G. Sersa; M. Cemazar. 2021. "Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma." Bioelectrochemistry 141, no. : 107843.
In order to provide insights into the evolutionary and epidemiological viral dynamics during the current COVID-19 pandemic in South Eastern Italy, a total of 298 genomes of SARS-CoV-2 strains collected in the Apulia and Basilicata regions, between March 2020 and January 2021, were sequenced. The genomic analysis performed on the draft genomes allowed us to assign the genetic clades and lineages of belonging to each sample and provide an overview of the main circulating viral variants. Our data showed the spread in Apulia and Basilicata of SARS-CoV-2 variants which have emerged during the second wave of infections and are being currently monitored worldwide for their increased transmission rate and their possible impact on vaccines and therapies. These results emphasize the importance of genome sequencing for the epidemiological surveillance of the new SARS-CoV-2 variants’ spread.
Loredana Capozzi; Angelica Bianco; Laura Del Sambro; Domenico Simone; Antonio Lippolis; Maria Notarnicola; Graziano Pesole; Lorenzo Pace; Domenico Galante; Antonio Parisi. Genomic Surveillance of Circulating SARS-CoV-2 in South East Italy: A One-Year Retrospective Genetic Study. Viruses 2021, 13, 731 .
AMA StyleLoredana Capozzi, Angelica Bianco, Laura Del Sambro, Domenico Simone, Antonio Lippolis, Maria Notarnicola, Graziano Pesole, Lorenzo Pace, Domenico Galante, Antonio Parisi. Genomic Surveillance of Circulating SARS-CoV-2 in South East Italy: A One-Year Retrospective Genetic Study. Viruses. 2021; 13 (5):731.
Chicago/Turabian StyleLoredana Capozzi; Angelica Bianco; Laura Del Sambro; Domenico Simone; Antonio Lippolis; Maria Notarnicola; Graziano Pesole; Lorenzo Pace; Domenico Galante; Antonio Parisi. 2021. "Genomic Surveillance of Circulating SARS-CoV-2 in South East Italy: A One-Year Retrospective Genetic Study." Viruses 13, no. 5: 731.
SARS-CoV-2 replication requires the synthesis of a set of structural proteins expressed through discontinuous transcription of ten subgenomic mRNAs (sgmRNAs). Here, we have fine-tuned a droplet digital PCR (ddPCR) assays to accurately detect and quantify SARS-CoV-2 genomic ORF1ab and sgmRNAs for the nucleocapsid (N) and spike (S) proteins. We analyzed 166 RNAs from anonymized COVID-19 positive subjects and we found a recurrent and characteristic pattern of sgmRNAs expression in relation to the total viral RNA content. Further, we observed that expression profiles of sgmRNAs analyzed in a subset of 110 samples subjected to meta-transcriptomics sequencing were highly correlated with those obtained by ddPCR. Our results, providing a comprehensive and dynamic snapshot of SARS-CoV-2 sgmRNAs expression and replication, may contribute to provide a better understanding of SARS-CoV-2 transcription and expression mechanisms, and support the development of more accurate molecular diagnostic tools and for the stratification of COVID-19 patients.
Annarita Oranger; Caterina Manzari; Matteo Chiara; Elisabetta Notario; Bruno Fosso; Antonio Parisi; Angelica Bianco; Michela Iacobellis; Morena D'Avenia; Anna Maria D'Erchia; Graziano Pesole. Accurate detection and quantification of SARS-CoV-2 genomic and subgenomic mRNAs by ddPCR and meta-transcriptomics analysis. 2021, 1 .
AMA StyleAnnarita Oranger, Caterina Manzari, Matteo Chiara, Elisabetta Notario, Bruno Fosso, Antonio Parisi, Angelica Bianco, Michela Iacobellis, Morena D'Avenia, Anna Maria D'Erchia, Graziano Pesole. Accurate detection and quantification of SARS-CoV-2 genomic and subgenomic mRNAs by ddPCR and meta-transcriptomics analysis. . 2021; ():1.
Chicago/Turabian StyleAnnarita Oranger; Caterina Manzari; Matteo Chiara; Elisabetta Notario; Bruno Fosso; Antonio Parisi; Angelica Bianco; Michela Iacobellis; Morena D'Avenia; Anna Maria D'Erchia; Graziano Pesole. 2021. "Accurate detection and quantification of SARS-CoV-2 genomic and subgenomic mRNAs by ddPCR and meta-transcriptomics analysis." , no. : 1.
The superfamily of TRIM (TRIpartite Motif-containing) proteins is one of the largest groups of E3 ubiquitin ligases. Among them, interest in TRIM8 has greatly increased in recent years. In this review, we analyze the regulation of TRIM8 gene expression and how it is involved in many cell reactions in response to different stimuli such as genotoxic stress and attacks by viruses or bacteria, playing a central role in the immune response and orchestrating various fundamental biological processes such as cell survival, carcinogenesis, autophagy, apoptosis, differentiation and inflammation. Moreover, we show how TRIM8 functions are not limited to ubiquitination, and contrasting data highlight its role either as an oncogene or as a tumor suppressor gene, acting as a “double-edged weapon”. This is linked to its involvement in the selective regulation of three pivotal cellular signaling pathways: the p53 tumor suppressor, NF-κB and JAK-STAT pathways. Lastly, we describe how TRIM8 dysfunctions are linked to inflammatory processes, autoimmune disorders, rare developmental and cardiovascular diseases, ischemia, intellectual disability and cancer.
Flaviana Marzano; Luisa Guerrini; Graziano Pesole; Elisabetta Sbisà; Apollonia Tullo. Emerging Roles of TRIM8 in Health and Disease. Cells 2021, 10, 561 .
AMA StyleFlaviana Marzano, Luisa Guerrini, Graziano Pesole, Elisabetta Sbisà, Apollonia Tullo. Emerging Roles of TRIM8 in Health and Disease. Cells. 2021; 10 (3):561.
Chicago/Turabian StyleFlaviana Marzano; Luisa Guerrini; Graziano Pesole; Elisabetta Sbisà; Apollonia Tullo. 2021. "Emerging Roles of TRIM8 in Health and Disease." Cells 10, no. 3: 561.
Colorectal cancer (CRC) initiation is believed to result from the conversion of normal intestinal stem cells (ISCs) into cancer stem cells (CSCs), also known as tumor-initiating cells (TICs). Hence, CRC evolves through the multiple acquisition of well-established genetic and epigenetic alterations with an adenoma-carcinoma sequence progression. Unlike other stem cells elsewhere in the body, ISCs cohabit with the intestinal microbiota, which consists of a diverse community of microorganisms, including bacteria, fungi, and viruses. The gut microbiota communicates closely with ISCs and mounting evidence suggests that there is significant crosstalk between host and microbiota at the ISC niche level. Metagenomic analyses have demonstrated that the host-microbiota mutually beneficial symbiosis existing under physiologic conditions is lost during a state of pathological microbial imbalance due to the alteration of microbiota composition (dysbiosis) and/or the genetic susceptibility of the host. The complex interaction between CRC and microbiota is at the forefront of the current CRC research, and there is growing attention on a possible role of the gut microbiome in the pathogenesis of CRC through ISC niche impairment. Here we primarily review the most recent findings on the molecular mechanism underlying the complex interplay between gut microbiota and ISCs, revealing a possible key role of microbiota in the aberrant reprogramming of CSCs in the initiation of CRC. We also discuss recent advances in OMICS approaches and single-cell analyses to explore the relationship between gut microbiota and ISC/CSC niche biology leading to a desirable implementation of the current precision medicine approaches.
Marinella Marzano; Bruno Fosso; Elisabetta Piancone; Giuseppe Defazio; Graziano Pesole; Mariangela De Robertis. Stem Cell Impairment at the Host-Microbiota Interface in Colorectal Cancer. Cancers 2021, 13, 996 .
AMA StyleMarinella Marzano, Bruno Fosso, Elisabetta Piancone, Giuseppe Defazio, Graziano Pesole, Mariangela De Robertis. Stem Cell Impairment at the Host-Microbiota Interface in Colorectal Cancer. Cancers. 2021; 13 (5):996.
Chicago/Turabian StyleMarinella Marzano; Bruno Fosso; Elisabetta Piancone; Giuseppe Defazio; Graziano Pesole; Mariangela De Robertis. 2021. "Stem Cell Impairment at the Host-Microbiota Interface in Colorectal Cancer." Cancers 13, no. 5: 996.
Colorectal cancer (CRC) represents one of the most widespread forms of cancer in the population and, as all malignant tumors, often develops resistance to chemotherapies with consequent tumor growth and spreading leading to the patient’s premature death. For this reason, a great challenge is to identify new therapeutic targets, able to restore the drugs sensitivity of cancer cells. In this review, we discuss the role of TRIpartite Motifs (TRIM) proteins in cancers and in CRC chemoresistance, focusing on the tumor-suppressor role of TRIM8 protein in the reactivation of the CRC cells sensitivity to drugs currently used in the clinical practice. Since the restoration of TRIM8 protein levels in CRC cells recovers chemotherapy response, it may represent a new promising therapeutic target in the treatment of CRC.
Flaviana Marzano; Mariano Caratozzolo; Graziano Pesole; Elisabetta Sbisà; Apollonia Tullo. TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance. Biomedicines 2021, 9, 241 .
AMA StyleFlaviana Marzano, Mariano Caratozzolo, Graziano Pesole, Elisabetta Sbisà, Apollonia Tullo. TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance. Biomedicines. 2021; 9 (3):241.
Chicago/Turabian StyleFlaviana Marzano; Mariano Caratozzolo; Graziano Pesole; Elisabetta Sbisà; Apollonia Tullo. 2021. "TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance." Biomedicines 9, no. 3: 241.
Effective systems for the analysis of molecular data are fundamental for monitoring the spread of infectious diseases and studying pathogen evolution. The rapid identification of emerging viral strains, and/or genetic variants potentially associated with novel phenotypic features is one of the most important objectives of genomic surveillance of human pathogens and represents one of the first lines of defense for the control of their spread. During the COVID 19 pandemic, several taxonomic frameworks have been proposed for the classification of SARS-Cov-2 isolates. These systems, which are typically based on phylogenetic approaches, represent essential tools for epidemiological studies as well as contributing to the study of the origin of the outbreak. Here, we propose an alternative, reproducible, and transparent phenetic method to study changes in SARS-CoV-2 genomic diversity over time. We suggest that our approach can complement other systems and facilitate the identification of biologically relevant variants in the viral genome. To demonstrate the validity of our approach, we present comparative genomic analyses of more than 175,000 genomes. Our method delineates 22 distinct SARS-CoV-2 haplogroups, which, based on the distribution of high-frequency genetic variants, fall into four major macrohaplogroups. We highlight biased spatiotemporal distributions of SARS-CoV-2 genetic profiles and show that seven of the 22 haplogroups (and of all of the four haplogroup clusters) showed a broad geographic distribution within China by the time the outbreak was widely recognized—suggesting early emergence and widespread cryptic circulation of the virus well before its isolation in January 2020. General patterns of genomic variability are remarkably similar within all major SARS-CoV-2 haplogroups, with UTRs consistently exhibiting the greatest variability, with s2m, a conserved secondary structure element of unknown function in the 3′-UTR of the viral genome showing evidence of a functional shift. Although several polymorphic sites that are specific to one or more haplogroups were predicted to be under positive or negative selection, overall our analyses suggest that the emergence of novel types is unlikely to be driven by convergent evolution and independent fixation of advantageous substitutions, or by selection of recombined strains. In the absence of extensive clinical metadata for most available genome sequences, and in the context of extensive geographic and temporal biases in the sampling, many questions regarding the evolution and clinical characteristics of SARS-CoV-2 isolates remain open. However, our data indicate that the approach outlined here can be usefully employed in the identification of candidate SARS-CoV-2 genetic variants of clinical and epidemiological importance.
Matteo Chiara; David S Horner; Carmela Gissi; Graziano Pesole. Comparative Genomics Reveals Early Emergence and Biased Spatiotemporal Distribution of SARS-CoV-2. Molecular Biology and Evolution 2021, 1 .
AMA StyleMatteo Chiara, David S Horner, Carmela Gissi, Graziano Pesole. Comparative Genomics Reveals Early Emergence and Biased Spatiotemporal Distribution of SARS-CoV-2. Molecular Biology and Evolution. 2021; ():1.
Chicago/Turabian StyleMatteo Chiara; David S Horner; Carmela Gissi; Graziano Pesole. 2021. "Comparative Genomics Reveals Early Emergence and Biased Spatiotemporal Distribution of SARS-CoV-2." Molecular Biology and Evolution , no. : 1.
Staphylococcus cohnii (SC), a coagulase-negative bacterium, was first isolated in 1975 from human skin. Early phenotypic analyses led to the delineation of two subspecies (subsp.), Staphylococcus cohnii subsp. cohnii (SCC) and Staphylococcus cohnii subsp. urealyticus (SCU). SCC was considered to be specific to humans, whereas SCU apparently demonstrated a wider host range, from lower primates to humans. The type strains ATCC 29974 and ATCC 49330 have been designated for SCC and SCU, respectively. Comparative analysis of 66 complete genome sequences—including a novel SC isolate—revealed unexpected patterns within the SC complex, both in terms of genomic sequence identity and gene content, highlighting the presence of 3 phylogenetically distinct groups. Based on our observations, and on the current guidelines for taxonomic classification for bacterial species, we propose a revision of the SC species complex. We suggest that SCC and SCU should be regarded as two distinct species: SC and SU (Staphylococcus urealyticus), and that two distinct subspecies, SCC and SCB (SC subsp. barensis, represented by the novel strain isolated in Bari) should be recognized within SC. Furthermore, since large-scale comparative genomics studies recurrently suggest inconsistencies or conflicts in taxonomic assignments of bacterial species, we believe that the approach proposed here might be considered for more general application.
Anna Lavecchia; Matteo Chiara; Caterina De Virgilio; Caterina Manzari; Carlo Pazzani; David Horner; Graziano Pesole; Antonio Placido. Comparative Genomics Suggests a Taxonomic Revision of the Staphylococcus cohnii Species Complex. Genome Biology and Evolution 2021, 13, 1 .
AMA StyleAnna Lavecchia, Matteo Chiara, Caterina De Virgilio, Caterina Manzari, Carlo Pazzani, David Horner, Graziano Pesole, Antonio Placido. Comparative Genomics Suggests a Taxonomic Revision of the Staphylococcus cohnii Species Complex. Genome Biology and Evolution. 2021; 13 (4):1.
Chicago/Turabian StyleAnna Lavecchia; Matteo Chiara; Caterina De Virgilio; Caterina Manzari; Carlo Pazzani; David Horner; Graziano Pesole; Antonio Placido. 2021. "Comparative Genomics Suggests a Taxonomic Revision of the Staphylococcus cohnii Species Complex." Genome Biology and Evolution 13, no. 4: 1.
In diploid organisms, two copies of each allele are normally inherited from parents. Paternal and maternal alleles can be regulated and expressed unequally, which is referred to as allele-specific expression (ASE). In this work, we present aScan, a novel method for the identification of ASE from the analysis of matched individual genomic and RNA sequencing data. By performing extensive analyses of both real and simulated data, we demonstrate that aScan can correctly identify ASE with high accuracy and sensitivity in different experimental settings. Additionally, by applying our method to a small cohort of individuals that are not included in publicly available databases of human genetic variation, we outline the value of possible applications of ASE analysis in single individuals for deriving a more accurate annotation of “private” low-frequency genetic variants associated with regulatory effects on transcription. All in all, we believe that aScan will represent a beneficial addition to the set of bioinformatics tools for the analysis of ASE. Finally, while our method was initially conceived for the analysis of RNA-seq data, it can in principle be applied to any quantitative NGS assay for which matched genotypic and expression data are available. aScan is currently available in the form of an open source standalone software package at: https://github.com/Federico77z/aScan/. aScan version 1.0.3, available at https://github.com/Federico77z/aScan/releases/tag/1.0.3, has been used for all the analyses included in this manuscript. A Docker image of the tool has also been made available at https://github.com/pmandreoli/aScanDocker.
Federico Zambelli; Matteo Chiara; Erika Ferrandi; Pietro Mandreoli; Marco Antonio Tangaro; Giulio Pavesi; Graziano Pesole. aScan: A Novel Method for the Study of Allele Specific Expression in Single Individuals. Journal of Molecular Biology 2021, 433, 166829 .
AMA StyleFederico Zambelli, Matteo Chiara, Erika Ferrandi, Pietro Mandreoli, Marco Antonio Tangaro, Giulio Pavesi, Graziano Pesole. aScan: A Novel Method for the Study of Allele Specific Expression in Single Individuals. Journal of Molecular Biology. 2021; 433 (11):166829.
Chicago/Turabian StyleFederico Zambelli; Matteo Chiara; Erika Ferrandi; Pietro Mandreoli; Marco Antonio Tangaro; Giulio Pavesi; Graziano Pesole. 2021. "aScan: A Novel Method for the Study of Allele Specific Expression in Single Individuals." Journal of Molecular Biology 433, no. 11: 166829.
The Yes-associated protein (YAP), one of the major effectors of the Hippo pathway together with its related protein WW-domain-containing transcription regulator 1 (WWTR1; also known as TAZ), mediates a range of cellular processes from proliferation and death to morphogenesis. YAP and WW-domain-containing transcription regulator 1 (WWTR1; also known as TAZ) regulate a large number of target genes, acting as coactivators of DNA-binding transcription factors or as negative regulators of transcription by interacting with the nucleosome remodeling and histone deacetylase complexes. YAP is expressed in self-renewing embryonic stem cells (ESCs), although it is still debated whether it plays any crucial roles in the control of either stemness or differentiation. Here we show that the transient downregulation of YAP in mouse ESCs perturbs cellular homeostasis, leading to the inability to differentiate properly. Bisulfite genomic sequencing revealed that this transient knockdown caused a genome-wide alteration of the DNA methylation remodeling that takes place during the early steps of differentiation, suggesting that the phenotype we observed might be due to the dysregulation of some of the mechanisms involved in regulation of ESC exit from pluripotency. By gene expression analysis, we identified two molecules that could have a role in the altered genome-wide methylation profile: the long noncoding RNA ephemeron, whose rapid upregulation is crucial for the transition of ESCs into epiblast, and the methyltransferase-like protein Dnmt3l, which, during the embryo development, cooperates with Dnmt3a and Dnmt3b to contribute to the de novo DNA methylation that governs early steps of ESC differentiation. These data suggest a new role for YAP in the governance of the epigenetic dynamics of exit from pluripotency.
Fabiana Passaro; Ilaria De Martino; Federico Zambelli; Giorgia Di Benedetto; Matteo Barbato; Anna Maria D’Erchia; Caterina Manzari; Graziano Pesole; Margherita Mutarelli; Davide Cacchiarelli; Dario Antonini; Silvia Parisi; Tommaso Russo. YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation. Journal of Biological Chemistry 2021, 296, 100138 .
AMA StyleFabiana Passaro, Ilaria De Martino, Federico Zambelli, Giorgia Di Benedetto, Matteo Barbato, Anna Maria D’Erchia, Caterina Manzari, Graziano Pesole, Margherita Mutarelli, Davide Cacchiarelli, Dario Antonini, Silvia Parisi, Tommaso Russo. YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation. Journal of Biological Chemistry. 2021; 296 ():100138.
Chicago/Turabian StyleFabiana Passaro; Ilaria De Martino; Federico Zambelli; Giorgia Di Benedetto; Matteo Barbato; Anna Maria D’Erchia; Caterina Manzari; Graziano Pesole; Margherita Mutarelli; Davide Cacchiarelli; Dario Antonini; Silvia Parisi; Tommaso Russo. 2021. "YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation." Journal of Biological Chemistry 296, no. : 100138.
Motivation Clinical applications of genome re-sequencing technologies typically generate large amounts of data that need to be carefully annotated and interpreted to identify genetic variants potentially associated with pathological conditions. In this context, accurate and reproducible methods for the functional annotation and prioritization of genetic variants are of fundamental importance. Results In this article, we present VINYL, a flexible and fully automated system for the functional annotation and prioritization of genetic variants. Extensive analyses of both real and simulated datasets suggest that VINYL can identify clinically relevant genetic variants in a more accurate manner compared to equivalent state of the art methods, allowing a more rapid and effective prioritization of genetic variants in different experimental settings. As such we believe that VINYL can establish itself as a valuable tool to assist healthcare operators and researchers in clinical genomics investigations. Availability and implementation VINYL is available at http://beaconlab.it/VINYL and https://github.com/matteo14c/VINYL. Supplementary information Supplementary data are available at Bioinformatics online.
Matteo Chiara; Pietro Mandreoli; Marco Antonio Tangaro; Anna Maria D'Erchia; Sandro Sorrentino; Cinzia Forleo; David S Horner; Federico Zambelli; Graziano Pesole. VINYL: Variant prIoritizatioN bY survivaL analysis. Bioinformatics 2020, 1 .
AMA StyleMatteo Chiara, Pietro Mandreoli, Marco Antonio Tangaro, Anna Maria D'Erchia, Sandro Sorrentino, Cinzia Forleo, David S Horner, Federico Zambelli, Graziano Pesole. VINYL: Variant prIoritizatioN bY survivaL analysis. Bioinformatics. 2020; ():1.
Chicago/Turabian StyleMatteo Chiara; Pietro Mandreoli; Marco Antonio Tangaro; Anna Maria D'Erchia; Sandro Sorrentino; Cinzia Forleo; David S Horner; Federico Zambelli; Graziano Pesole. 2020. "VINYL: Variant prIoritizatioN bY survivaL analysis." Bioinformatics , no. : 1.
Various next generation sequencing (NGS) based strategies have been successfully used in the recent past for tracing origins and understanding the evolution of infectious agents, investigating the spread and transmission chains of outbreaks, as well as facilitating the development of effective and rapid molecular diagnostic tests and contributing to the hunt for treatments and vaccines. The ongoing COVID-19 pandemic poses one of the greatest global threats in modern history and has already caused severe social and economic costs. The development of efficient and rapid sequencing methods to reconstruct the genomic sequence of SARS-CoV-2, the etiological agent of COVID-19, has been fundamental for the design of diagnostic molecular tests and to devise effective measures and strategies to mitigate the diffusion of the pandemic. Diverse approaches and sequencing methods can, as testified by the number of available sequences, be applied to SARS-CoV-2 genomes. However, each technology and sequencing approach has its own advantages and limitations. In the current review, we will provide a brief, but hopefully comprehensive, account of currently available platforms and methodological approaches for the sequencing of SARS-CoV-2 genomes. We also present an outline of current repositories and databases that provide access to SARS-CoV-2 genomic data and associated metadata. Finally, we offer general advice and guidelines for the appropriate sharing and deposition of SARS-CoV-2 data and metadata, and suggest that more efficient and standardized integration of current and future SARS-CoV-2-related data would greatly facilitate the struggle against this new pathogen. We hope that our ‘vademecum’ for the production and handling of SARS-CoV-2-related sequencing data, will contribute to this objective.
Matteo Chiara; Anna Maria D’Erchia; Carmela Gissi; Caterina Manzari; Antonio Parisi; Nicoletta Resta; Federico Zambelli; Ernesto Picardi; Giulio Pavesi; David S Horner; Graziano Pesole. Next generation sequencing of SARS-CoV-2 genomes: challenges, applications and opportunities. Briefings in Bioinformatics 2020, 22, 616 -630.
AMA StyleMatteo Chiara, Anna Maria D’Erchia, Carmela Gissi, Caterina Manzari, Antonio Parisi, Nicoletta Resta, Federico Zambelli, Ernesto Picardi, Giulio Pavesi, David S Horner, Graziano Pesole. Next generation sequencing of SARS-CoV-2 genomes: challenges, applications and opportunities. Briefings in Bioinformatics. 2020; 22 (2):616-630.
Chicago/Turabian StyleMatteo Chiara; Anna Maria D’Erchia; Carmela Gissi; Caterina Manzari; Antonio Parisi; Nicoletta Resta; Federico Zambelli; Ernesto Picardi; Giulio Pavesi; David S Horner; Graziano Pesole. 2020. "Next generation sequencing of SARS-CoV-2 genomes: challenges, applications and opportunities." Briefings in Bioinformatics 22, no. 2: 616-630.
The artificial introduction in the soil of antagonistic microorganisms can be a successful strategy, alternative to agrochemicals, for the control of the root-knot nematodes (Meloidogyne spp.) and for preserving plant health. On the other hand, plant roots and the associated rhizosphere constitute a complex system in which the contribution of microbial community is fundamental to plant health and development, since microbes may convert organic and inorganic substances into available plant nutrients. In the present study, the potential nematicidal activity of the biopesticide Aphanocladium album (A. album strain MX-95) against the root-knot nematode Meloidogyne javanica in infected tomato plants was investigated. Specifically, the effect of the A. album treatment on plant fitness was evaluated observing the plant morphological traits and also considering the nematode propagation parameters, the A. album MX-95 vitality and population density. In addition, the treatment effects on the rhizosphere microbiome were analysed by a metabarcoding procedure. Treatments with A. album isolate MX-95 significantly decreased root gall severity index and soil nematode population. The treatment also resulted in increased rhizosphere microbial populations. A. album MX-95 can be favourably considered as a new bionematicide to control M. javanica infestation.
Claudia Leoni; Elisabetta Piancone; Nicola Sasanelli; Giovanni Luigi Bruno; Caterina Manzari; Graziano Pesole; Luigi R. Ceci; Mariateresa Volpicella. Plant Health and Rhizosphere Microbiome: Effects of the Bionematicide Aphanocladium album in Tomato Plants Infested by Meloidogyne javanica. Microorganisms 2020, 8, 1922 .
AMA StyleClaudia Leoni, Elisabetta Piancone, Nicola Sasanelli, Giovanni Luigi Bruno, Caterina Manzari, Graziano Pesole, Luigi R. Ceci, Mariateresa Volpicella. Plant Health and Rhizosphere Microbiome: Effects of the Bionematicide Aphanocladium album in Tomato Plants Infested by Meloidogyne javanica. Microorganisms. 2020; 8 (12):1922.
Chicago/Turabian StyleClaudia Leoni; Elisabetta Piancone; Nicola Sasanelli; Giovanni Luigi Bruno; Caterina Manzari; Graziano Pesole; Luigi R. Ceci; Mariateresa Volpicella. 2020. "Plant Health and Rhizosphere Microbiome: Effects of the Bionematicide Aphanocladium album in Tomato Plants Infested by Meloidogyne javanica." Microorganisms 8, no. 12: 1922.
Summary While over 200 000 genomic sequences are currently available through dedicated repositories, ad hoc methods for the functional annotation of SARS-CoV-2 genomes do not harness all currently available resources for the annotation of functionally relevant genomic sites. Here, we present CorGAT, a novel tool for the functional annotation of SARS-CoV-2 genomic variants. By comparisons with other state of the art methods we demonstrate that, by providing a more comprehensive and rich annotation, our method can facilitate the identification of evolutionary patterns in the genome of SARS-CoV-2. Availabilityand implementation Galaxy http://corgat.cloud.ba.infn.it/galaxy; software: https://github.com/matteo14c/CorGAT/tree/Revision_V1; docker: https://hub.docker.com/r/laniakeacloud/galaxy_corgat. Supplementary information Supplementary data are available at Bioinformatics online.
Matteo Chiara; Federico Zambelli; Marco Antonio Tangaro; Pietro Mandreoli; David S Horner; Graziano Pesole. CorGAT: a tool for the functional annotation of SARS-CoV-2 genomes. Bioinformatics 2020, 36, 5522 -5523.
AMA StyleMatteo Chiara, Federico Zambelli, Marco Antonio Tangaro, Pietro Mandreoli, David S Horner, Graziano Pesole. CorGAT: a tool for the functional annotation of SARS-CoV-2 genomes. Bioinformatics. 2020; 36 (22-23):5522-5523.
Chicago/Turabian StyleMatteo Chiara; Federico Zambelli; Marco Antonio Tangaro; Pietro Mandreoli; David S Horner; Graziano Pesole. 2020. "CorGAT: a tool for the functional annotation of SARS-CoV-2 genomes." Bioinformatics 36, no. 22-23: 5522-5523.
RNA editing is a relevant epitranscriptome phenomenon able to increase the transcriptome and proteome diversity of eukaryotic organisms. ADAR mediated RNA editing is widespread in humans in which millions of A-to-I changes modify thousands of primary transcripts. RNA editing has pivotal roles in the regulation of gene expression or modulation of the innate immune response or functioning of several neurotransmitter receptors. Massive transcriptome sequencing has fostered the research in this field. Nonetheless, different aspects of the RNA editing biology are still unknown and need to be elucidated. To support the study of A-to-I RNA editing we have updated our REDIportal catalogue raising its content to about 16 millions of events detected in 9642 human RNAseq samples from the GTEx project by using a dedicated pipeline based on the HPC version of the REDItools software. REDIportal now allows searches at sample level, provides overviews of RNA editing profiles per each RNAseq experiment, implements a Gene View module to look at individual events in their genic context and hosts the CLAIRE database. Starting from this novel version, REDIportal will start collecting non-human RNA editing changes for comparative genomics investigations. The database is freely available at http://srv00.recas.ba.infn.it/atlas/index.html.
Luigi Mansi; Marco Antonio Tangaro; Claudio Lo Giudice; Tiziano Flati; Eli Kopel; Amos Avraham Schaffer; Tiziana Castrignanò; Giovanni Chillemi; Graziano Pesole; Ernesto Picardi. REDIportal: millions of novel A-to-I RNA editing events from thousands of RNAseq experiments. Nucleic Acids Research 2020, 49, D1012 -D1019.
AMA StyleLuigi Mansi, Marco Antonio Tangaro, Claudio Lo Giudice, Tiziano Flati, Eli Kopel, Amos Avraham Schaffer, Tiziana Castrignanò, Giovanni Chillemi, Graziano Pesole, Ernesto Picardi. REDIportal: millions of novel A-to-I RNA editing events from thousands of RNAseq experiments. Nucleic Acids Research. 2020; 49 (D1):D1012-D1019.
Chicago/Turabian StyleLuigi Mansi; Marco Antonio Tangaro; Claudio Lo Giudice; Tiziano Flati; Eli Kopel; Amos Avraham Schaffer; Tiziana Castrignanò; Giovanni Chillemi; Graziano Pesole; Ernesto Picardi. 2020. "REDIportal: millions of novel A-to-I RNA editing events from thousands of RNAseq experiments." Nucleic Acids Research 49, no. D1: D1012-D1019.
The quantification of the total microbial content in metagenomic samples is critical for investigating the interplay between the microbiome and its host, as well as for assessing the accuracy and precision of the relative microbial composition which can be strongly biased in low microbial biomass samples. In the present study, we demonstrate that digital droplet PCR (ddPCR) can provide accurate quantification of the total copy number of the 16S rRNA gene, the gene usually exploited for assessing total bacterial abundance in metagenomic DNA samples. Notably, using DNA templates with different integrity levels, as measured by the DNA integrity number (DIN), we demonstrated that 16S rRNA copy number quantification is strongly affected by DNA quality and determined a precise correlation between quantification underestimation and DNA degradation levels. Therefore, we propose an input DNA mass correction, according to the observed DIN value, which could prevent inaccurate quantification of 16S copy number in degraded metagenomic DNAs. Our results highlight that a preliminary evaluation of the metagenomic DNA integrity should be considered before performing metagenomic analyses of different samples, both for the assessment of the reliability of observed differential abundances in different conditions and to obtain significant functional insights.
Caterina Manzari; Annarita Oranger; Bruno Fosso; Elisabetta Piancone; Graziano Pesole; Anna Maria D’Erchia. Accurate quantification of bacterial abundance in metagenomic DNAs accounting for variable DNA integrity levels. Microbial Genomics 2020, 6, e000417 .
AMA StyleCaterina Manzari, Annarita Oranger, Bruno Fosso, Elisabetta Piancone, Graziano Pesole, Anna Maria D’Erchia. Accurate quantification of bacterial abundance in metagenomic DNAs accounting for variable DNA integrity levels. Microbial Genomics. 2020; 6 (10):e000417.
Chicago/Turabian StyleCaterina Manzari; Annarita Oranger; Bruno Fosso; Elisabetta Piancone; Graziano Pesole; Anna Maria D’Erchia. 2020. "Accurate quantification of bacterial abundance in metagenomic DNAs accounting for variable DNA integrity levels." Microbial Genomics 6, no. 10: e000417.
Background RNA editing is a widespread co-/post-transcriptional mechanism that alters primary RNA sequences through the modification of specific nucleotides and it can increase both the transcriptome and proteome diversity. The automatic detection of RNA-editing from RNA-seq data is computational intensive and limited to small data sets, thus preventing a reliable genome-wide characterisation of such process. Results In this work we introduce HPC-REDItools, an upgraded tool for accurate RNA-editing events discovery from large dataset repositories. Availability: https://github.com/BioinfoUNIBA/REDItools2. Conclusions HPC-REDItools is dramatically faster than the previous version, REDItools, enabling big-data analysis by means of a MPI-based implementation and scaling almost linearly with the number of available cores.
Tiziano Flati; Silvia Gioiosa; Nicola Spallanzani; Ilario Tagliaferri; Maria Angela Diroma; Graziano Pesole; Giovanni Chillemi; Ernesto Picardi; Tiziana Castrignanò. HPC-REDItools: a novel HPC-aware tool for improved large scale RNA-editing analysis. BMC Bioinformatics 2020, 21, 1 -12.
AMA StyleTiziano Flati, Silvia Gioiosa, Nicola Spallanzani, Ilario Tagliaferri, Maria Angela Diroma, Graziano Pesole, Giovanni Chillemi, Ernesto Picardi, Tiziana Castrignanò. HPC-REDItools: a novel HPC-aware tool for improved large scale RNA-editing analysis. BMC Bioinformatics. 2020; 21 (10):1-12.
Chicago/Turabian StyleTiziano Flati; Silvia Gioiosa; Nicola Spallanzani; Ilario Tagliaferri; Maria Angela Diroma; Graziano Pesole; Giovanni Chillemi; Ernesto Picardi; Tiziana Castrignanò. 2020. "HPC-REDItools: a novel HPC-aware tool for improved large scale RNA-editing analysis." BMC Bioinformatics 21, no. 10: 1-12.
Background The advent of Next Generation Sequencing (NGS) technologies and the concomitant reduction in sequencing costs allows unprecedented high throughput profiling of biological systems in a cost-efficient manner. Modern biological experiments are increasingly becoming both data and computationally intensive and the wealth of publicly available biological data is introducing bioinformatics into the “Big Data” era. For these reasons, the effective application of High Performance Computing (HPC) architectures is becoming progressively more recognized also by bioinformaticians. Here we describe HPC resources provisioning pilot programs dedicated to bioinformaticians, run by the Italian Node of ELIXIR (ELIXIR-IT) in collaboration with CINECA, the main Italian supercomputing center. Results Starting from April 2016, CINECA and ELIXIR-IT launched the pilot Call “ELIXIR-IT [email protected]”, offering streamlined access to HPC resources for bioinformatics. Resources are made available either through web front-ends to dedicated workflows developed at CINECA or by providing direct access to the High Performance Computing systems through a standard command-line interface tailored for bioinformatics data analysis. This allows to offer to the biomedical research community a production scale environment, continuously updated with the latest available versions of publicly available reference datasets and bioinformatic tools. Currently, 63 research projects have gained access to the [email protected] program, for a total handout of ~ 8 Millions of CPU/hours and, for data storage, ~ 100 TB of permanent and ~ 300 TB of temporary space. Conclusions Three years after the beginning of the ELIXIR-IT [email protected] program, we can appreciate its impact over the Italian bioinformatics community and draw some considerations. Several Italian researchers who applied to the program have gained access to one of the top-ranking public scientific supercomputing facilities in Europe. Those investigators had the opportunity to sensibly reduce computational turnaround times in their research projects and to process massive amounts of data, pursuing research approaches that would have been otherwise difficult or impossible to undertake. Moreover, by taking advantage of the wealth of documentation and training material provided by CINECA, participants had the opportunity to improve their skills in the usage of HPC systems and be better positioned to apply to similar EU programs of greater scale, such as PRACE. To illustrate the effective usage and impact of the resources awarded by the program - in different research applications - we report five successful use cases, which have already published their findings in peer-reviewed journals.
Tiziana Castrignanò; Silvia Gioiosa; Tiziano Flati; Mirko Cestari; Ernesto Picardi; Matteo Chiara; Maddalena Fratelli; Stefano Amente; Marco Cirilli; Marco Antonio Tangaro; Giovanni Chillemi; Graziano Pesole; Federico Zambelli. ELIXIR-IT [email protected]: high performance computing resources for the bioinformatics community. BMC Bioinformatics 2020, 21, 1 -17.
AMA StyleTiziana Castrignanò, Silvia Gioiosa, Tiziano Flati, Mirko Cestari, Ernesto Picardi, Matteo Chiara, Maddalena Fratelli, Stefano Amente, Marco Cirilli, Marco Antonio Tangaro, Giovanni Chillemi, Graziano Pesole, Federico Zambelli. ELIXIR-IT [email protected]: high performance computing resources for the bioinformatics community. BMC Bioinformatics. 2020; 21 (10):1-17.
Chicago/Turabian StyleTiziana Castrignanò; Silvia Gioiosa; Tiziano Flati; Mirko Cestari; Ernesto Picardi; Matteo Chiara; Maddalena Fratelli; Stefano Amente; Marco Cirilli; Marco Antonio Tangaro; Giovanni Chillemi; Graziano Pesole; Federico Zambelli. 2020. "ELIXIR-IT [email protected]: high performance computing resources for the bioinformatics community." BMC Bioinformatics 21, no. 10: 1-17.