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1.
J Cardiovasc Dev Dis ; 8(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209143

RESUMO

AIMS: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. METHODS AND RESULTS: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. CONCLUSIONS: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.

2.
Comput Struct Biotechnol J ; 19: 4092-4100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306570

RESUMO

Motivation: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. While ageing has been extensively demonstrated to be accompanied by some modifications at the gene expression level, a possible link with COVID-19 manifestation still need to be investigated at the molecular level. Objectives: This study aims to shed out light on a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people. Methods: We considered public datasets of ageing-related genes and their expression at the tissue level. We selected human proteins interacting with viral ones that are known to be related to the ageing process. Finally, we investigated changes in the expression level of coding genes at the tissue, gender and age level. Results: We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes, suggesting that those genes are particularly affected by COVID-19 infection. Our analysis evidenced that virus infection particularly involves ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4. We found that HMGA1 and NPM1 have different expressions in the lung of males, while HMGA1, APEX1, CHEK1, EEF2, and NPM1 present changes in expression in males due to ageing effects. Conclusion: Our study generated a mechanistic framework to clarify the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. We also provide testable hypotheses for future investigation and pharmacological solutions tailored to specific age ranges.

3.
J Med Virol ; 93(9): 5638-5643, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33951211

RESUMO

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, posing a renewed threat to coronavirus disease 2019 containment and to vaccine and drug efficacy. In this study, we analyzed more than 1,000,000 SARS-CoV-2 genomic sequences deposited up to April 27, 2021, on the GISAID public repository, and identified a novel T478K mutation located on the SARS-CoV-2 Spike protein. The mutation is structurally located in the region of interaction with human receptor ACE2 and was detected in 11,435 distinct cases. We show that T478K has appeared and risen in frequency since January 2021, predominantly in Mexico and the United States, but we could also detect it in several European countries.


Assuntos
COVID-19/virologia , Genoma Viral , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/fisiologia , Europa (Continente) , Humanos , México , Mutação , Filogenia , Glicoproteína da Espícula de Coronavírus/genética , Estados Unidos
4.
Cancers (Basel) ; 13(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918978

RESUMO

Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.

5.
ChemMedChem ; 16(15): 2315-2329, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33890721

RESUMO

Copper is an essential transition metal frequently increased in cancer known to strongly influence essential cellular processes. Targeted therapy protocols utilizing both novel and repurposed drug agents initially demonstrate strong efficacy, before failing in advanced cancers as drug resistance develops and relapse occurs. Overcoming this limitation involves the development of strategies and protocols aimed at a wider targeting of the underlying molecular changes. Receptor Tyrosine Kinase signaling pathways, epigenetic mechanisms and cell metabolism are among the most common therapeutic targets, with molecular investigations increasingly demonstrating the strong influence each mechanism exerts on the others. Interestingly, all these mechanisms can be influenced by intracellular copper. We propose that copper chelating agents, already in clinical trial for multiple cancers, may simultaneously target these mechanisms across a wide variety of cancers, serving as an excellent candidate for targeted combination therapy. This review summarizes the known links between these mechanisms, copper, and copper chelation therapy.

6.
Cell Rep ; 35(2): 108994, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852836

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable childhood brain tumor for which new treatments are needed. CBL0137 is an anti-cancer compound developed from quinacrine that targets facilitates chromatin transcription (FACT), a chromatin remodeling complex involved in transcription, replication, and DNA repair. We show that CBL0137 displays profound cytotoxic activity against a panel of patient-derived DIPG cultures by restoring tumor suppressor TP53 and Rb activity. Moreover, in an orthotopic model of DIPG, treatment with CBL0137 significantly extends animal survival. The FACT subunit SPT16 is found to directly interact with H3.3K27M, and treatment with CBL0137 restores both histone H3 acetylation and trimethylation. Combined treatment of CBL0137 with the histone deacetylase inhibitor panobinostat leads to inhibition of the Rb/E2F1 pathway and induction of apoptosis. The combination of CBL0137 and panobinostat significantly prolongs the survival of mice bearing DIPG orthografts, suggesting a potential treatment strategy for DIPG.

7.
Cell ; 184(2): 334-351.e20, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33434495

RESUMO

Despite considerable efforts, the mechanisms linking genomic alterations to the transcriptional identity of cancer cells remain elusive. Integrative genomic analysis, using a network-based approach, identified 407 master regulator (MR) proteins responsible for canalizing the genetics of individual samples from 20 cohorts in The Cancer Genome Atlas (TCGA) into 112 transcriptionally distinct tumor subtypes. MR proteins could be further organized into 24 pan-cancer, master regulator block modules (MRBs), each regulating key cancer hallmarks and predictive of patient outcome in multiple cohorts. Of all somatic alterations detected in each individual sample, >50% were predicted to induce aberrant MR activity, yielding insight into mechanisms linking tumor genetics and transcriptional identity and establishing non-oncogene dependencies. Genetic and pharmacological validation assays confirmed the predicted effect of upstream mutations and MR activity on downstream cellular identity and phenotype. Thus, co-analysis of mutational and gene expression profiles identified elusive subtypes and provided testable hypothesis for mechanisms mediating the effect of genetic alterations.


Assuntos
Neoplasias/genética , Transcrição Genética , Adenocarcinoma/genética , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Genoma Humano , Células HEK293 , Humanos , Camundongos Nus , Mutação/genética , Reprodutibilidade dos Testes
8.
Nat Biotechnol ; 39(2): 215-224, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32929263

RESUMO

Tumor-specific elucidation of physical and functional oncoprotein interactions could improve tumorigenic mechanism characterization and therapeutic response prediction. Current interaction models and pathways, however, lack context specificity and are not oncoprotein specific. We introduce SigMaps as context-specific networks, comprising modulators, effectors and cognate binding-partners of a specific oncoprotein. SigMaps are reconstructed de novo by integrating diverse evidence sources-including protein structure, gene expression and mutational profiles-via the OncoSig machine learning framework. We first generated a KRAS-specific SigMap for lung adenocarcinoma, which recapitulated published KRAS biology, identified novel synthetic lethal proteins that were experimentally validated in three-dimensional spheroid models and established uncharacterized crosstalk with RAB/RHO. To show that OncoSig is generalizable, we first inferred SigMaps for the ten most mutated human oncoproteins and then for the full repertoire of 715 proteins in the COSMIC Cancer Gene Census. Taken together, these SigMaps show that the cell's regulatory and signaling architecture is highly tissue specific.


Assuntos
Redes Reguladoras de Genes , Neoplasias/genética , Proteínas Oncogênicas/metabolismo , Algoritmos , Animais , Humanos , Camundongos , Mutação/genética , Organoides/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Interferente Pequeno/metabolismo , Curva ROC , Transdução de Sinais
9.
J Med Virol ; 93(5): 3238-3245, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33205830

RESUMO

The avalanche of genomic data generated from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus requires the development of tools to detect and monitor its mutations across the world. Here, we present a webtool, coronapp, dedicated to easily processing user-provided SARS-CoV-2 genomic sequences and visualizing the current worldwide status of SARS-CoV-2 mutations. The webtool allows users to highlight mutations and categorize them by frequency, country, genomic location and effect on protein sequences, and to monitor their presence in the population over time. The tool is available at http://giorgilab.unibo.it/coronannotator/ for the annotation of user-provided sequences. The full code is freely shared at https://github.com/federicogiorgi/giorgilab/tree/master/coronannotator.


Assuntos
Genoma Viral , Mutação , SARS-CoV-2/genética , Sequência de Aminoácidos , COVID-19/virologia , Genômica , Humanos
10.
Brief Bioinform ; 22(2): 690-700, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33057582

RESUMO

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.


Assuntos
COVID-19/prevenção & controle , Pandemias , COVID-19/virologia , Biologia Computacional , Humanos , Internet , SARS-CoV-2/isolamento & purificação
11.
Bioinformatics ; 37(13): 1912-1914, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-33051644

RESUMO

MOTIVATION: Despite widespread prevalence of somatic structural variations (SVs) across most tumor types, understanding of their molecular implications often remains poor. SVs are extremely heterogeneous in size and complexity, hindering the interpretation of their pathogenic role. Tools integrating large SV datasets across platforms are required to fully characterize the cancer's somatic landscape. RESULTS: svpluscnv R package is a swiss army knife for the integration and interpretation of orthogonal datasets including copy number variant segmentation profiles and sequencing-based structural variant calls. The package implements analysis and visualization tools to evaluate chromosomal instability and ploidy, identify genes harboring recurrent SVs and detects complex rearrangements such as chromothripsis and chromoplexia. Further, it allows systematic identification of hot-spot shattered genomic regions, showing reproducibility across alternative detection methods and datasets. AVAILABILITY AND IMPLEMENTATION: https://github.com/ccbiolab/svpluscnv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Genoma , Genômica , Variações do Número de Cópias de DNA , Variação Estrutural do Genoma , Humanos , Reprodutibilidade dos Testes , Análise de Sequência , Software
12.
Genes Immun ; 21(5): 360-363, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33011745

RESUMO

Pulpitis, inflammation of the dental pulp, is a disease that often necessitates emergency dental care. While pulpitis is considered to be a microbial disease primarily caused by bacteria, viruses have also been implicated in its pathogenesis. Here, we determined the expression of the SARS-CoV2 receptor, angiotensin converting enzyme 2 (ACE2) and its associated cellular serine protease TPMRSS2 in the dental pulp under normal and inflamed conditions. Next, we explored the relationship between the SARS-CoV-2/human interactome and genes expressed in pulpitis. Using existing datasets we show that both ACE2 and TPMRSS2 are expressed in the dental pulp and, that their expression does not change under conditions of inflammation. Furthermore, Master Regulator Analysis of the SARS-CoV2/human interactome identified 75 relevant genes whose expression values are either up-regulated or down-regulated in both the human interactome and pulpitis. Our results suggest that the dental pulp is vulnerable to SARS-CoV2 infection and that SARS-CoV-2 infection of the dental pulp may contribute to worse outcomes of pulpitis.


Assuntos
Infecções por Coronavirus/complicações , Polpa Dentária/metabolismo , Pneumonia Viral/complicações , Pulpite/virologia , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/metabolismo , COVID-19 , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Conjuntos de Dados como Assunto , Polpa Dentária/virologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Pulpite/metabolismo , Receptores de Coronavírus , Receptores Virais/metabolismo , SARS-CoV-2 , Serina Endopeptidases/metabolismo
13.
Cancer Res ; 80(19): 4129-4144, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32816860

RESUMO

Therapeutic checkpoint antibodies blocking programmed death receptor 1/programmed death ligand 1 (PD-L1) signaling have radically improved clinical outcomes in cancer. However, the regulation of PD-L1 expression on tumor cells is still poorly understood. Here we show that intratumoral copper levels influence PD-L1 expression in cancer cells. Deep analysis of the The Cancer Genome Atlas database and tissue microarrays showed strong correlation between the major copper influx transporter copper transporter 1 (CTR-1) and PD-L1 expression across many cancers but not in corresponding normal tissues. Copper supplementation enhanced PD-L1 expression at mRNA and protein levels in cancer cells and RNA sequencing revealed that copper regulates key signaling pathways mediating PD-L1-driven cancer immune evasion. Conversely, copper chelators inhibited phosphorylation of STAT3 and EGFR and promoted ubiquitin-mediated degradation of PD-L1. Copper-chelating drugs also significantly increased the number of tumor-infiltrating CD8+ T and natural killer cells, slowed tumor growth, and improved mouse survival. Overall, this study reveals an important role for copper in regulating PD-L1 and suggests that anticancer immunotherapy might be enhanced by pharmacologically reducing intratumor copper levels. SIGNIFICANCE: These findings characterize the role of copper in modulating PD-L1 expression and contributing to cancer immune evasion, highlighting the potential for repurposing copper chelators as enhancers of antitumor immunity. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/19/4129/F1.large.jpg.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/imunologia , Cobre/metabolismo , Neuroblastoma/imunologia , Evasão Tumoral/fisiologia , Animais , Antígeno B7-H1/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Quelantes/farmacologia , Transportador de Cobre 1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia/métodos , Células Matadoras Naturais , Linfócitos do Interstício Tumoral/patologia , Camundongos Endogâmicos BALB C , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Trietilenofosforamida/farmacologia , Evasão Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Front Microbiol ; 11: 1800, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793182

RESUMO

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.

15.
Plant J ; 104(4): 979-994, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32860440

RESUMO

Plants need to attune their stress responses to the ongoing developmental programmes to maximize their efficacy. For instance, successful submergence adaptation is often associated with a delicate balance between saving resources and their expenditure to activate measures that allow stress avoidance or attenuation. We observed a significant decrease in submergence tolerance associated with ageing in Arabidopsis thaliana, with a critical step between 2 and 3 weeks of post-germination development. This sensitization to flooding was concomitant with the transition from juvenility to adulthood. Transcriptomic analyses indicated that a group of genes related to abscisic acid and oxidative stress response was more highly expressed in juvenile plants than in adult ones. These genes are induced by the endomembrane tethered transcription factor ANAC017 that was in turn activated by submergence-associated oxidative stress. A combination of molecular, biochemical and genetic analyses showed that these genes are located in genomic regions that move towards a heterochromatic state with adulthood, as marked by lysine 4 trimethylation of histone H3. We concluded that, while the mechanisms of flooding stress perception and signal transduction were unaltered between juvenile and adult phases, the sensitivity that these mechanisms set into action is integrated, via epigenetic regulation, into the developmental programme of the plant.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Epigênese Genética , Oxigênio/metabolismo , Fatores de Transcrição/metabolismo , Ácido Abscísico/metabolismo , Adaptação Fisiológica , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Perfilação da Expressão Gênica , Germinação , Estresse Oxidativo , Reguladores de Crescimento de Plantas/metabolismo , Plantas Geneticamente Modificadas , Estresse Fisiológico , Fatores de Transcrição/genética
16.
Toxicology ; 441: 152531, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32593706

RESUMO

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.


Assuntos
Redes Reguladoras de Genes/efeitos dos fármacos , Leucemia/metabolismo , Proteínas Inativadoras de Ribossomos/farmacologia , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Lectinas/farmacologia , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , N-Glicosil Hidrolases/farmacologia , Toxina Shiga I/farmacologia , Fatores de Transcrição/metabolismo
17.
Genes (Basel) ; 11(5)2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429325

RESUMO

Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling and gene expression profiles. We provide here a review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents. We will investigate the chemical specificity of different HDACs and discuss their role in the human interactome as members of chromatin-binding and regulatory complexes.


Assuntos
Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/genética , Neoplasias/genética , Fatores de Transcrição/genética , Antineoplásicos/uso terapêutico , Histonas/genética , Humanos , Neoplasias/terapia , Especificidade por Substrato/genética
18.
Bioinformatics ; 36(17): 4664-4667, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437522

RESUMO

SUMMARY: A primary problem in high-throughput genomics experiments is finding the most important genes involved in biological processes (e.g. tumor progression). In this applications note, we introduce spathial, an R package for navigating high-dimensional data spaces. spathial implements the Principal Path algorithm, which is a topological method for locally navigating on the data manifold. The package, together with the core algorithm, provides several high-level functions for interpreting the results. One of the analyses we propose is the extraction of the genes that are mainly involved in the progress from one state to another. We show a possible application in the context of tumor progression using RNA-Seq and single-cell datasets, and we compare our results with two commonly used algorithms, edgeR and monocle3, respectively. AVAILABILITY AND IMPLEMENTATION: The R package spathial is available on the Comprehensive R Archive Network (https://cran.r-project.org/web/packages/spathial/index.html) and on GitHub (https://github.com/erikagardini/spathial). It is distributed under the GNU General Public License (version 3). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Evolução Biológica , Genômica
19.
Bioinformatics ; 36(12): 3916-3917, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32232425

RESUMO

MOTIVATION: Gene network inference and master regulator analysis (MRA) have been widely adopted to define specific transcriptional perturbations from gene expression signatures. Several tools exist to perform such analyses but most require a computer cluster or large amounts of RAM to be executed. RESULTS: We developed corto, a fast and lightweight R package to infer gene networks and perform MRA from gene expression data, with optional corrections for copy-number variations and able to run on signatures generated from RNA-Seq or ATAC-Seq data. We extensively benchmarked it to infer context-specific gene networks in 39 human tumor and 27 normal tissue datasets. AVAILABILITY AND IMPLEMENTATION: Cross-platform and multi-threaded R package on CRAN (stable version) https://cran.r-project.org/package=corto and Github (development release) https://github.com/federicogiorgi/corto. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Redes Reguladoras de Genes , Neoplasias , Humanos , Software , Transcriptoma
20.
J Clin Med ; 9(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244779

RESUMO

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.

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