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Article ; Online: Gene network reverse engineering: The Next Generation.

Giorgi, Federico M

Biochimica et biophysica acta. Gene regulatory mechanisms

2020 Volume 1863, Issue 6, Page(s) 194523

MeSH term(s)	Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Transcription Factors/metabolism
Chemical Substances	Transcription Factors
Language	English
Publishing date	2020-03-05
Publishing country	Netherlands
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2918786-2
ISSN	1876-4320 ; 1874-9399
ISSN (online)	1876-4320
ISSN	1874-9399
DOI	10.1016/j.bbagrm.2020.194523
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Article ; Online: Genomic and transcriptomic analysis of the recent Mpox outbreak.

Giorgi, Federico M / Pozzobon, Daniele / Di Meglio, Antonio / Mercatelli, Daniele

Vaccine

2024 Volume 42, Issue 7, Page(s) 1841–1849

Abstract: The Mpox (formerly named Monkeypox) virus is the etiological cause of a recent multi-country outbreak, with thousands of distinct cases detected outside the endemic areas of Africa as of December 2023. In this article, we analyze the sequences of full ... ...

Abstract	The Mpox (formerly named Monkeypox) virus is the etiological cause of a recent multi-country outbreak, with thousands of distinct cases detected outside the endemic areas of Africa as of December 2023. In this article, we analyze the sequences of full genomes of Mpox virus from Europe and compare them with all available Mpox sequences of historical relevance, annotated by year and geographic origin, as well as related Cowpox and Variola (smallpox) virus sequences. Our results show that the recent outbreak is most likely originating from the West African clade of Mpox, with >99 % sequence identity with sequences derived from historical and recent cases, dating from 1971 to 2017. We analyze specific mutations occurring in viral proteins between the current outbreak, previous Mpox and Cowpox sequences, and the historical Variola virus. Genome-wide sequence analysis of the recent outbreak and other Mpox/Cowpox/Variola viruses shows a very high conservation, with 97.9 % (protein-based) and 97.8 % (nucleotide-based) sequence identity. We identified significant correlation in human transcriptional responses as well, with a conserved immune pathway response induced in human cell cultures by the three families of Pox virus. The similarities identified between the major strains of Pox viruses, as well as within the Mpox clades, both at the genomic and transcriptomic levels, provide a molecular basis for the observed efficacy of Variola vaccines in other Poxviruses.
MeSH term(s)	Animals ; Humans ; Smallpox ; Cowpox ; Mpox (monkeypox)/epidemiology ; DNA, Viral/genetics ; Variola virus ; Poxviridae ; Monkeypox virus/genetics ; Genomics ; Disease Outbreaks ; Gene Expression Profiling
Chemical Substances	DNA, Viral
Language	English
Publishing date	2024-02-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.12.086
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Article ; Online: Single-Cell Sequencing Identifies Master Regulators Affected by Panobinostat in Neuroblastoma Cells.

Milazzo, Giorgio / Perini, Giovanni / Giorgi, Federico M

Genes

2022 Volume 13, Issue 12

Abstract: The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor ... ...

Abstract	The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor panobinostat, could be tested to mitigate tumor progression. Here, we set out to investigate the effects of panobinostat treatment at the unprecedented resolution offered by single-cell sequencing. We identified a global senescence signature paired with reduction in proliferation in treated Kelly cells and more isolated transcriptional responses compatible with early neuronal differentiation. Using master regulator analysis, we identified BAZ1A, HCFC1, MAZ, and ZNF146 as the transcriptional regulators most significantly repressed by panobinostat. Experimental silencing of these transcription factors (TFs) confirmed their role in sustaining NBL cell proliferation in vitro.
Language	English
Publishing date	2022-11-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13122240
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Article: The R Language: An Engine for Bioinformatics and Data Science.

Giorgi, Federico M / Ceraolo, Carmine / Mercatelli, Daniele

Life (Basel, Switzerland)

2022 Volume 12, Issue 5

Abstract: The R programming language is approaching its 30th birthday, and in the last three decades it has achieved a prominent role in statistics, bioinformatics, and data science in general. It currently ranks among the top 10 most popular languages worldwide, ... ...

Abstract	The R programming language is approaching its 30th birthday, and in the last three decades it has achieved a prominent role in statistics, bioinformatics, and data science in general. It currently ranks among the top 10 most popular languages worldwide, and its community has produced tens of thousands of extensions and packages, with scopes ranging from machine learning to transcriptome data analysis. In this review, we provide an historical chronicle of how R became what it is today, describing all its current features and capabilities. We also illustrate the major tools of R, such as the current R editors and integrated development environments (IDEs), the R Shiny web server, the R methods for machine learning, and its relationship with other programming languages. We also discuss the role of R in science in general as a driver for reproducibility. Overall, we hope to provide both a complete snapshot of R today and a practical compendium of the major features and applications of this programming language.
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12050648
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Article ; Online: Single-Cell Sequencing Identifies Master Regulators Affected by Panobinostat in Neuroblastoma Cells

Milazzo, Giorgio / Perini, Giovanni / Giorgi, Federico M.

Genes (Basel). 2022 Nov. 29, v. 13, no. 12

2022

Abstract	The molecular mechanisms and gene regulatory networks sustaining cell proliferation in neuroblastoma (NBL) cells are still not fully understood. In this tumor context, it has been proposed that anti-proliferative drugs, such as the pan-HDAC inhibitor panobinostat, could be tested to mitigate tumor progression. Here, we set out to investigate the effects of panobinostat treatment at the unprecedented resolution offered by single-cell sequencing. We identified a global senescence signature paired with reduction in proliferation in treated Kelly cells and more isolated transcriptional responses compatible with early neuronal differentiation. Using master regulator analysis, we identified BAZ1A, HCFC1, MAZ, and ZNF146 as the transcriptional regulators most significantly repressed by panobinostat. Experimental silencing of these transcription factors (TFs) confirmed their role in sustaining NBL cell proliferation in vitro.
Keywords	cell proliferation ; genes ; neoplasm progression ; neoplasms ; neurons ; transcription (genetics)
Language	English
Dates of publication	2022-1129
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13122240
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Genomic variance of the 2019-nCoV coronavirus.

Ceraolo, Carmine / Giorgi, Federico M

Journal of medical virology

2020 Volume 92, Issue 5, Page(s) 522–528

Abstract: There is a rising global concern for the recently emerged novel coronavirus (2019-nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular ... ...

Abstract	There is a rising global concern for the recently emerged novel coronavirus (2019-nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.
MeSH term(s)	Amino Acid Sequence ; Animals ; Base Sequence ; Betacoronavirus/classification ; Betacoronavirus/genetics ; COVID-19 ; Chiroptera/virology ; Coronavirus Infections/virology ; Genetic Variation ; Genome, Viral ; Humans ; Models, Genetic ; Phylogeny ; Pneumonia, Viral ; Proteome ; RNA, Viral/genetics ; SARS-CoV-2
Chemical Substances	Proteome ; RNA, Viral
Keywords	covid19
Language	English
Publishing date	2020-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.25700
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Article: Geographic and Genomic Distribution of SARS-CoV-2 Mutations.

Mercatelli, Daniele / Giorgi, Federico M

Frontiers in microbiology

2020 Volume 11, Page(s) 1800

Abstract: The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered ...

Abstract	The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered across the globe can underly geographically specific etiological effects. In the present study, we gather the 48,635 SARS-CoV-2 complete genomes currently available thanks to the collection endeavor of the GISAID consortium and thousands of contributing laboratories. We analyzed and annotated all SARS-CoV-2 mutations compared with the reference Wuhan genome NC_045512.2, observing an average of 7.23 mutations per sample. Our analysis shows the prevalence of single nucleotide transitions as the major mutational type across the world. There exist at least three clades characterized by geographic and genomic specificity. In particular, clade G, prevalent in Europe, carries a D614G mutation in the Spike protein, which is responsible for the initial interaction of the virus with the host human cell. Our analysis may facilitate custom-designed antiviral strategies based on the molecular specificities of SARS-CoV-2 in different patients and geographical locations.
Keywords	covid19
Language	English
Publishing date	2020-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2020.01800
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Article ; Online: Direct and indirect responses of the Arabidopsis transcriptome to an induced increase in trehalose 6-phosphate.

Avidan, Omri / Martins, Marina C M / Feil, Regina / Lohse, Marc / Giorgi, Federico M / Schlereth, Armin / Lunn, John E / Stitt, Mark

Plant physiology

2024

Abstract: Trehalose 6-phosphate (Tre6P) is an essential signal metabolite that regulates the level of sucrose, linking growth and development to the metabolic status. We hypothesized that Tre6P plays a role in mediating the regulation of gene expression by sucrose. ...

Abstract	Trehalose 6-phosphate (Tre6P) is an essential signal metabolite that regulates the level of sucrose, linking growth and development to the metabolic status. We hypothesized that Tre6P plays a role in mediating the regulation of gene expression by sucrose. To test this, we performed transcriptomic profiling on Arabidopsis (Arabidopsis thaliana) plants that expressed a bacterial TREHALOSE 6-PHOSPHATE SYNTHASE (TPS) under the control of an ethanol-inducible promoter. Induction led to a 4-fold rise in Tre6P levels, a concomitant decrease in sucrose, significant changes (FDR ≤ 0.05) of over 13,000 transcripts, and two-fold or larger changes of over 5000 transcripts. Comparison with nine published responses to sugar availability allowed some of these changes to be linked to the rise in Tre6P, while others were probably due to lower sucrose or other indirect effects. Changes linked to Tre6P included repression of photosynthesis-related gene expression and induction of many growth-related processes including ribosome biogenesis. About 500 starvation-related genes are known to be induced by SUCROSE-NON-FERMENTING-1-RELATED KINASE 1 (SnRK1). They were largely repressed by Tre6P in a manner consistent with SnRK1 inhibition by Tre6P. SnRK1 also represses many genes that are involved in biosynthesis and growth. These responded to Tre6P in a more complex manner, pointing toward Tre6P interacting with other C-signaling pathways. Additionally, elevated Tre6P modified the expression of genes encoding regulatory subunits of the SnRK1 complex and TPS class II and FCS-LIKE ZINC FINGER proteins that are thought to modulate SnRK1 function and genes involved in circadian, TARGET OF RAPAMYCIN-, light, abscisic acid, and other hormone signaling.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	208914-2
ISSN	1532-2548 ; 0032-0889
ISSN (online)	1532-2548
ISSN	0032-0889
DOI	10.1093/plphys/kiae196
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Article ; Online: Transcriptional network inference and master regulator analysis of the response to ribosome-inactivating proteins in leukemia cells.

Mercatelli, Daniele / Bortolotti, Massimo / Giorgi, Federico M

Toxicology

2020 Volume 441, Page(s) 152531

Abstract: Gene-regulatory networks reconstruction has become a very popular approach in applied biology to infer and dissect functional interactions of Transcription Factors (TFs) driving a defined phenotypic state, termed as Master Regulators (MRs). In the ... ...

Abstract	Gene-regulatory networks reconstruction has become a very popular approach in applied biology to infer and dissect functional interactions of Transcription Factors (TFs) driving a defined phenotypic state, termed as Master Regulators (MRs). In the present work, cutting-edge bioinformatic methods were applied to re-analyze experimental data on leukemia cells (human myelogenous leukemia cell line THP-1 and acute myeloid leukemia MOLM-13 cells) treated for 6 h with two different Ribosome-Inactivating Proteins (RIPs), namely Shiga toxin type 1 (400 ng/mL) produced by Escherichia coli strains and the plant toxin stenodactylin (60 ng/mL), purified from the caudex of Adenia stenodactyla Harms. This analysis allowed us to identify the common early transcriptional response to 28S rRNA damage based on gene-regulatory network inference and Master Regulator Analysis (MRA). Both toxins induce a common response at 6 h which involves inflammatory mediators triggered by AP-1 family transcriptional factors and ATF3 in leukemia cells. We describe for the first time the involvement of MAFF, KLF2 and KLF6 in regulating RIP-induced apoptotic cell death, while receptor-mediated downstream signaling through ANXA1 and TLR4 is suggested for both toxins.
MeSH term(s)	Cell Line, Tumor ; Gene Expression Regulation, Leukemic/drug effects ; Gene Regulatory Networks/drug effects ; Humans ; Lectins/pharmacology ; Leukemia/metabolism ; Membrane Proteins/drug effects ; Membrane Proteins/metabolism ; N-Glycosyl Hydrolases/pharmacology ; Ribosome Inactivating Proteins/pharmacology ; Shiga Toxin 1/pharmacology ; Transcription Factors/metabolism
Chemical Substances	Lectins ; Membrane Proteins ; Shiga Toxin 1 ; Transcription Factors ; N-Glycosyl Hydrolases (EC 3.2.2.-) ; stenodactylin protein, Adenia stenodactyla (EC 3.2.2.-) ; Ribosome Inactivating Proteins (EC 3.2.2.22)
Language	English
Publishing date	2020-06-25
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2020.152531
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Article ; Online: Web tools to fight pandemics: the COVID-19 experience.

Mercatelli, Daniele / Holding, Andrew N / Giorgi, Federico M

Briefings in bioinformatics

2020 Volume 22, Issue 2, Page(s) 690–700

Abstract: The current outbreak of COVID-19 has generated an unprecedented scientific response worldwide, with the generation of vast amounts of publicly available epidemiological, biological and clinical data. Bioinformatics scientists have quickly produced online ...

Abstract	The current outbreak of COVID-19 has generated an unprecedented scientific response worldwide, with the generation of vast amounts of publicly available epidemiological, biological and clinical data. Bioinformatics scientists have quickly produced online methods to provide non-computational users with the opportunity of analyzing such data. In this review, we report the results of this effort, by cataloguing the currently most popular web tools for COVID-19 research and analysis. Our focus was driven on tools drawing data from the fields of epidemiology, genomics, interactomics and pharmacology, in order to provide a meaningful depiction of the current state of the art of COVID-19 online resources.
MeSH term(s)	COVID-19/prevention & control ; COVID-19/virology ; Computational Biology ; Humans ; Internet ; Pandemics ; SARS-CoV-2/isolation & purification
Keywords	covid19
Language	English
Publishing date	2020-10-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2068142-2
ISSN	1477-4054 ; 1467-5463
ISSN (online)	1477-4054
ISSN	1467-5463
DOI	10.1093/bib/bbaa261
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