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1.
Brief Bioinform ; 22(6)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34010955

RESUMO

The complex web of macromolecular interactions occurring within cells-the interactome-is the backbone of an increasing number of studies, but a clear consensus on the exact structure of this network is still lacking. Different genome-scale maps of human interactome have been obtained through several experimental techniques and functional analyses. Moreover, these maps can be enriched through literature-mining approaches, and different combinations of various 'source' databases have been used in the literature. It is therefore unclear to which extent the various interactomes yield similar results when used in the context of interactome-based approaches in network biology. We compared a comprehensive list of human interactomes on the basis of topology, protein complexes, molecular pathways, pathway cross-talk and disease gene prediction. In a general context of relevant heterogeneity, our study provides a series of qualitative and quantitative parameters that describe the state of the art of human interactomes and guidelines for selecting interactomes in future applications.

2.
Viruses ; 13(5)2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922732

RESUMO

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7-82.3); p < 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4-6.2) log IU/mL vs. 5.3 (4.4-5.6) log IU/mL, p = 0.02) and lower ALT (35 (30-71) vs. 83 (48-108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and ß-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.


Assuntos
Carcinoma Hepatocelular/etiologia , Genótipo , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/virologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Proteínas não Estruturais Virais/genética , Idoso , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Suscetibilidade a Doenças , Feminino , Interações Hospedeiro-Patógeno , Humanos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Índice de Gravidade de Doença , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
4.
J Clin Oncol ; 39(11): 1223-1233, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33539200

RESUMO

PURPOSE: Recurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and prognostication. METHODS: We retrospectively enrolled 2,043 patients. Using Bayesian networks and Dirichlet processes, we combined mutations in 47 genes with cytogenetic abnormalities to identify genetic associations and subgroups. Random-effects Cox proportional hazards multistate modeling was used for developing prognostic models. An independent validation on 318 cases was performed. RESULTS: We identify eight MDS groups (clusters) according to specific genomic features. In five groups, dominant genomic features include splicing gene mutations (SF3B1, SRSF2, and U2AF1) that occur early in disease history, determine specific phenotypes, and drive disease evolution. These groups display different prognosis (groups with SF3B1 mutations being associated with better survival). Specific co-mutation patterns account for clinical heterogeneity within SF3B1- and SRSF2-related MDS. MDS with complex karyotype and/or TP53 gene abnormalities and MDS with acute leukemia-like mutations show poorest prognosis. MDS with 5q deletion are clustered into two distinct groups according to the number of mutated genes and/or presence of TP53 mutations. By integrating 63 clinical and genomic variables, we define a novel prognostic model that generates personally tailored predictions of survival. The predicted and observed outcomes correlate well in internal cross-validation and in an independent external cohort. This model substantially improves predictive accuracy of currently available prognostic tools. We have created a Web portal that allows outcome predictions to be generated for user-defined constellations of genomic and clinical features. CONCLUSION: Genomic landscape in MDS reveals distinct subgroups associated with specific clinical features and discrete patterns of evolution, providing a proof of concept for next-generation disease classification and prognosis.


Assuntos
Genômica/métodos , Síndromes Mielodisplásicas/classificação , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/genética , Prognóstico , Estudos Retrospectivos
5.
Neuroinformatics ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33506383

RESUMO

There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.

6.
Brain Sci ; 10(10)2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33081368

RESUMO

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response.

7.
Front Microbiol ; 11: 1808, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903390

RESUMO

Xylenes are considered one of the most common hazardous sources of environmental contamination. The biodegradation of these compounds has been often reported, rarer the ability to oxidize the ortho-isomer. Among few o-xylene-degrading bacteria, Rhodococcus opacus R7 is well known for its capability to degrade diverse aromatic hydrocarbons and toxic compounds, including o-xylene as only carbon and energy source. This work shows for the first time the RNA-seq approach to elucidate the genetic determinants involved in the o-xylene degradation pathway in R. opacus R7. Transcriptomic data showed 542 differentially expressed genes that are associated with the oxidation of aromatic hydrocarbons and stress response, osmotic regulation and central metabolism. Gene ontology (GO) enrichment and KEGG pathway analysis confirmed significant changes in aromatic compound catabolic processes, fatty acid metabolism, beta-oxidation, TCA cycle enzymes, and biosynthesis of metabolites when cells are cultured in the presence of o-xylene. Interestingly, the most up-regulated genes belong to the akb gene cluster encoding for the ethylbenzene (Akb) dioxygenase system. Moreover, the transcriptomic approach allowed identifying candidate enzymes involved in R7 o-xylene degradation for their likely participation in the formation of the metabolites that have been previously identified. Overall, this approach supports the identification of several oxidative systems likely involved in o-xylene metabolism confirming that R. opacus R7 possesses a redundancy of sequences that converge in o-xylene degradation through R7 peculiar degradation pathway. This work advances our understanding of o-xylene metabolism in bacteria belonging to Rhodococcus genus and provides a framework of useful enzymes (molecular tools) that can be fruitfully targeted for optimized o-xylene consumption.

8.
Front Immunol ; 11: 1426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754155

RESUMO

Monocytes and macrophages have a central role in all phases of an inflammatory reaction. To understanding the regulation of monocyte activation during a physiological or pathological inflammation, we propose two in vitro models that recapitulate the different phases of the reaction (recruitment, initiation, development, and resolution vs. persistence of inflammation), based on human primary blood monocytes exposed to sequential modifications of microenvironmental conditions. These models exclusively describe the functional development of blood-derived monocytes that first enter an inflammatory site. All reaction phases were profiled by RNA-Seq, and the two models were validated by studying the modulation of IL-1 family members. Genes were differentially modulated, and distinct clusters were identified during the various phases of inflammation. Pathway analysis revealed that both models were enriched in pathways involved in innate immune activation. We observe that monocytes acquire an M1-like profile during early inflammation, and switch to a deactivated M2-like profile during both the resolving and persistent phases. However, during persistent inflammation they partially maintain an M1 profile, although they lose the ability to produce inflammatory cytokines compared to M1 cells. The production of IL-1 family molecules by ELISA reflected the transcriptomic profiles in the distinct phases of the two inflammatory reactions. Based on the results, we hypothesize that persistence of inflammatory stimuli cannot maintain the M1 activated phenotype of incoming monocytes for long, suggesting that the persistent presence of M1 cells and effects in a chronically inflamed tissue is mainly due to activation of newly incoming cells. Moreover, being IL-1 family molecules mainly expressed and secreted by monocytes during the early stages of the inflammatory response (within 4-14 h), and the rate of their production decreasing during the late phase of both resolving and persistent inflammation, we suppose that IL-1 factors are key regulators of the acute defensive innate inflammatory reaction that precedes establishment of longer-term adaptive immunity, and are mainly related to the presence of recently recruited blood monocytes. The well-described role of IL-1 family cytokines and receptors in chronic inflammation is therefore most likely dependent on the continuous influx of blood monocytes into a chronically inflamed site.


Assuntos
Diferenciação Celular/imunologia , Inflamação/imunologia , Interleucina-1/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Humanos , Técnicas In Vitro
9.
Sci Rep ; 10(1): 7758, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385356

RESUMO

Gene-environment interactions, by means of abnormal macromolecular intestinal adsorption, is one of the possible causes of autism spectrum disorders (ASD) predominantly in patients with gastrointestinal disorders. Pre-haptoglobin-2 (zonulin), encoded by the Haptoglobin (HP) allele-2 gene, enhances the intestinal permeability by modulation of intercellular tight junctions. The two alleles of HP, HP1 and HP2, differ for 2 extra exons in HP2 that result in exon duplication undetectable by classic genome-wide association studies. To evaluate the role of HP2 in ASD pathogenesis and to set up a method to discriminate HP alleles, Italian subjects with ASD (n = 398) and healthy controls (n = 379) were genotyped by PCR analysis; subsequently, the PCR results were integrated with microarray genotypes (Illumina Human Omni 1S-8), obtained using a subset from the same subjects, and then we developed a computational method to predict HP alleles. On the contrary to our expectations, there was no association between HP2 and ASD (P > 0.05), and there was no significant allele association in subjects with ASD with or without gastrointestinal disorders (P > 0.05). With the aid of bioinformatics analysis, from a window frame of ~2 Mb containing 314 SNPs, we obtain imputation accuracy (r2) between 0.4 and 0.9 (median 0.7) and correct predictions were between 70% and 100% (median 90%). The conclusions endorse that enhanced intestinal permeability in subjects with ASD should not be imputed to HP2 but to other members of the zonulin family and/or to environmental factors.


Assuntos
Alelos , Transtorno do Espectro Autista/genética , Haptoglobinas/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
10.
Front Genet ; 11: 106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32180795

RESUMO

The development of integrative methods is one of the main challenges in bioinformatics. Network-based methods for the analysis of multiple gene-centered datasets take into account known and/or inferred relations between genes. In the last decades, the mathematical machinery of network diffusion-also referred to as network propagation-has been exploited in several network-based pipelines, thanks to its ability of amplifying association between genes that lie in network proximity. Indeed, network diffusion provides a quantitative estimation of network proximity between genes associated with one or more different data types, from simple binary vectors to real vectors. Therefore, this powerful data transformation method has also been increasingly used in integrative analyses of multiple collections of biological scores and/or one or more interaction networks. We present an overview of the state of the art of bioinformatics pipelines that use network diffusion processes for the integrative analysis of omics data. We discuss the fundamental ways in which network diffusion is exploited, open issues and potential developments in the field. Current trends suggest that network diffusion is a tool of broad utility in omics data analysis. It is reasonable to think that it will continue to be used and further refined as new data types arise (e.g. single cell datasets) and the identification of system-level patterns will be considered more and more important in omics data analysis.

11.
Sci Rep ; 10(1): 2643, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060296

RESUMO

In recent years complex networks have been identified as powerful mathematical frameworks for the adequate modeling of many applied problems in disparate research fields. Assuming a Master Equation (ME) modeling the exchange of information within the network, we set up a perturbative approach in order to investigate how node alterations impact on the network information flow. The main assumption of the perturbed ME (pME) model is that the simultaneous presence of multiple node alterations causes more or less intense network frailties depending on the specific features of the perturbation. In this perspective the collective behavior of a set of molecular alterations on a gene network is a particularly adapt scenario for a first application of the proposed method, since most diseases are neither related to a single mutation nor to an established set of molecular alterations. Therefore, after characterizing the method numerically, we applied as a proof of principle the pME approach to breast cancer (BC) somatic mutation data downloaded from Cancer Genome Atlas (TCGA) database. For each patient we measured the network frailness of over 90 significant subnetworks of the protein-protein interaction network, where each perturbation was defined by patient-specific somatic mutations. Interestingly the frailness measures depend on the position of the alterations on the gene network more than on their amount, unlike most traditional enrichment scores. In particular low-degree mutations play an important role in causing high frailness measures. The potential applicability of the proposed method is wide and suggests future development in the control theory context.


Assuntos
Redes Reguladoras de Genes , Modelos Genéticos , Mutação/genética , Apoptose/genética , Neoplasias da Mama/genética , Feminino , Humanos , Processos Estocásticos
12.
mSphere ; 5(1)2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32102941

RESUMO

Human body microbes interact with the host, forming microbial communities that are in continual flux during the aging process. Previous studies have mostly focused on surveying a single body habitat to determine the age-related variation in the bacterial and fungal communities. A more comprehensive understanding of the variation in the human microbiota and mycobiota across multiple body habitats related to aging is still unclear. To obtain an integrated view of the spatial distribution of microbes in a specific Mediterranean population across a wide age range, we surveyed the bacterial and fungal communities in the skin, oral cavity, and gut in the young, elderly, and centenarians in Sardinia using 16S rRNA gene and internal transcribed spacer 1 (ITS1) sequencing. We found that the distribution and correlation of bacterial and fungal communities in Sardinians were largely determined by body site. In each age group, the bacterial and fungal communities found in the skin were significantly different in structure. In the oral cavity, age had a marginal impact on the structures of the bacterial and fungal communities. Furthermore, the gut bacterial communities in centenarians clustered separately from those of the young and elderly, while the fungal communities in the gut habitat could not be separated by host age.IMPORTANCE Site-specific microbial communities are recognized as important factors in host health and disease. To better understand how the human microbiota potentially affects and is affected by its host during the aging process, the fundamental issue to address is the distribution of microbiota related to age. Here, we show an integrated view of the spatial distribution of microbes in a specific Mediterranean population (Sardinians) across a wide age range. Our study indicates that age plays a critical role in shaping the human microbiota in a habitat-dependent manner. The dynamic age-related microbiota changes we observed across multiple body sites may provide possibilities for modulating microbe communities to maintain or improve health during aging.


Assuntos
Fatores Etários , Envelhecimento , Bactérias/classificação , Fungos/genética , Microbiota , Micobioma , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Intergênico/genética , Ecossistema , Fezes/microbiologia , Feminino , Fungos/classificação , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Humanos , Itália , Masculino , Boca/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Pele/microbiologia , Adulto Jovem
13.
Bioinformatics ; 36(3): 865-871, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504182

RESUMO

MOTIVATION: Multi-omics approaches offer the opportunity to reconstruct a more complete picture of the molecular events associated with human diseases, but pose challenges in data analysis. Network-based methods for the analysis of multi-omics leverage the complex web of macromolecular interactions occurring within cells to extract significant patterns of molecular alterations. Existing network-based approaches typically address specific combinations of omics and are limited in terms of the number of layers that can be jointly analysed. In this study, we investigate the application of network diffusion to quantify gene relevance on the basis of multiple evidences (layers). RESULTS: We introduce a gene score (mND) that quantifies the relevance of a gene in a biological process taking into account the network proximity of the gene and its first neighbours to other altered genes. We show that mND has a better performance over existing methods in finding altered genes in network proximity in one or more layers. We also report good performances in recovering known cancer genes. The pipeline described in this article is broadly applicable, because it can handle different types of inputs: in addition to multi-omics datasets, datasets that are stratified in many classes (e.g., cell clusters emerging from single cell analyses) or a combination of the two scenarios. AVAILABILITY AND IMPLEMENTATION: The R package 'mND' is available at URL: https://www.itb.cnr.it/mnd. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , Humanos
14.
Bioinformatics ; 36(5): 1622-1624, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589304

RESUMO

SUMMARY: Retroviruses and their vector derivatives integrate semi-randomly in the genome of host cells and are inherited by their progeny as stable genetic marks. The retrieval and mapping of the sequences flanking the virus-host DNA junctions allows the identification of insertion sites in gene therapy or virally infected patients, essential for monitoring the evolution of genetically modified cells in vivo. However, since ∼30% of insertions land in low complexity or repetitive regions of the host cell genome, they cannot be correctly assigned and are currently discarded, limiting the accuracy and predictive power of clonal tracking studies. Here, we present γ-TRIS, a new graph-based genome-free alignment tool for identifying insertion sites even if embedded in low complexity regions. By using γ-TRIS to reanalyze clinical studies, we observed improvements in clonal quantification and tracking. AVAILABILITY AND IMPLEMENTATION: Source code at https://bitbucket.org/bereste/g-tris. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Genoma , Genômica , Algoritmos , Sequência de Bases , Humanos , Software
15.
EMBO Mol Med ; 12(1): e11019, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31793167

RESUMO

Duchenne muscular dystrophy (DMD) is a debilitating fatal X-linked muscle disorder. Recent findings indicate that IGFs play a central role in skeletal muscle regeneration and development. Among IGFs, insulinlike growth factor 2 (IGF2) is a key regulator of cell growth, survival, migration and differentiation. The type 2 IGF receptor (IGF2R) modulates circulating and tissue levels of IGF2 by targeting it to lysosomes for degradation. We found that IGF2R and the store-operated Ca2+ channel CD20 share a common hydrophobic binding motif that stabilizes their association. Silencing CD20 decreased myoblast differentiation, whereas blockade of IGF2R increased proliferation and differentiation in myoblasts via the calmodulin/calcineurin/NFAT pathway. Remarkably, anti-IGF2R induced CD20 phosphorylation, leading to the activation of sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase (SERCA) and removal of intracellular Ca2+ . Interestingly, we found that IGF2R expression was increased in dystrophic skeletal muscle of human DMD patients and mdx mice. Blockade of IGF2R by neutralizing antibodies stimulated muscle regeneration, induced force recovery and normalized capillary architecture in dystrophic mdx mice representing an encouraging starting point for the development of new biological therapies for DMD.


Assuntos
Músculo Esquelético/crescimento & desenvolvimento , Distrofia Muscular de Duchenne/tratamento farmacológico , Receptor IGF Tipo 2/antagonistas & inibidores , Regeneração , Animais , Sítios de Ligação , Criança , Humanos , Camundongos , Camundongos Endogâmicos mdx , Mioblastos , Adulto Jovem
16.
Sci Rep ; 9(1): 15768, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673058

RESUMO

p17 matrix protein released by HIV+ cells interacts with leukocytes heparan sulfate proteoglycans (HSPGs), CXCR1 and CXCR2 exerting different cytokine-like activities that contribute to AIDS pathogenesis. Since the bioactive form of several cytokines is represented by dimers/oligomers and oligomerization is promoted by binding to heparin or HSPGs, here we evaluated if heparin/HSPGs also promote p17 oligomerization. Heparin favours p17 dimer, trimer and tetramer assembly, in a time- and biphasic dose-dependent way. Heparin-induced p17 oligomerization is of electrostatic nature, being it prevented by NaCl, by removing negative sulfated groups of heparin and by neutralizing positive lysine residues in the p17 N-terminus. A new computational protocol has been implemented to study heparin chains up to 24-mer accommodating a p17 dimer. Molecular dynamics show that, in the presence of heparin, two p17 molecules undergo conformational modifications creating a continuous "electropositive channel" in which heparin sulfated groups interact with p17 basic amino acids, promoting its dimerization. At the cell surface, HSPGs induce p17 oligomerization, as demonstrated by using B-lymphoblastoid Namalwa cells overexpressing the HSPG Syndecan-1. Also, HSPGs on the surface of BJAB and Raji human B-lymphoblastoid cells are required to p17 to induce ERK1/2 activation, suggesting that HS-induced oligomerization plays a role in p17-induced lymphoid dysregulation during AIDS.


Assuntos
Síndrome de Imunodeficiência Adquirida/metabolismo , Antígenos HIV , HIV-1 , Sistema de Sinalização das MAP Quinases , Multimerização Proteica , Sindecana-1 , Produtos do Gene gag do Vírus da Imunodeficiência Humana , Linhagem Celular Tumoral , Antígenos HIV/química , Antígenos HIV/metabolismo , HIV-1/química , HIV-1/metabolismo , Heparina/química , Heparina/metabolismo , Humanos , Sindecana-1/química , Sindecana-1/metabolismo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
17.
Int J Mol Sci ; 20(13)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31323926

RESUMO

Current studies suggest that autism spectrum disorders (ASDs) may be caused by many genetic factors. In fact, collectively considering multiple studies aimed at characterizing the basic pathophysiology of ASDs, a large number of genes has been proposed. Addressing the problem of molecular data interpretation using gene networks helps to explain genetic heterogeneity in terms of shared pathways. Besides, the integrative analysis of multiple omics has emerged as an approach to provide a more comprehensive view of a disease. In this work, we carry out a network-based meta-analysis of the genes reported as associated with ASDs by studies that involved genomics, epigenomics, and transcriptomics. Collectively, our analysis provides a prioritization of the large number of genes proposed to be associated with ASDs, based on genes' relevance within the intracellular circuits, the strength of the supporting evidence of association with ASDs, and the number of different molecular alterations affecting genes. We discuss the presence of the prioritized genes in the SFARI (Simons Foundation Autism Research Initiative) database and in gene networks associated with ASDs by other investigations. Lastly, we provide the full results of our analyses to encourage further studies on common targets amenable to therapy.


Assuntos
Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Epigenômica/métodos , Genômica/métodos , Transcriptoma/genética , Biologia Computacional , Humanos
19.
Nat Genet ; 51(5): 885-895, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962619

RESUMO

The domestication of wild emmer wheat led to the selection of modern durum wheat, grown mainly for pasta production. We describe the 10.45 gigabase (Gb) assembly of the genome of durum wheat cultivar Svevo. The assembly enabled genome-wide genetic diversity analyses revealing the changes imposed by thousands of years of empirical selection and breeding. Regions exhibiting strong signatures of genetic divergence associated with domestication and breeding were widespread in the genome with several major diversity losses in the pericentromeric regions. A locus on chromosome 5B carries a gene encoding a metal transporter (TdHMA3-B1) with a non-functional variant causing high accumulation of cadmium in grain. The high-cadmium allele, widespread among durum cultivars but undetected in wild emmer accessions, increased in frequency from domesticated emmer to modern durum wheat. The rapid cloning of TdHMA3-B1 rescues a wild beneficial allele and demonstrates the practical use of the Svevo genome for wheat improvement.


Assuntos
Triticum/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Cádmio/metabolismo , Cromossomos de Plantas/genética , Domesticação , Variação Genética , Genoma de Planta , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Seleção Genética , Sintenia , Tetraploidia , Triticum/classificação , Triticum/metabolismo
20.
BMC Bioinformatics ; 20(Suppl 4): 125, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999855

RESUMO

The 17th International NETTAB workshop was held in Palermo, Italy, on October 16-18, 2017. The special topic for the meeting was "Methods, tools and platforms for Personalised Medicine in the Big Data Era", but the traditional topics of the meeting series were also included in the event. About 40 scientific contributions were presented, including four keynote lectures, five guest lectures, and many oral communications and posters. Also, three tutorials were organised before and after the workshop. Full papers from some of the best works presented in Palermo were submitted for this Supplement of BMC Bioinformatics. Here, we provide an overview of meeting aims and scope. We also shortly introduce selected papers that have been accepted for publication in this Supplement, for a complete presentation of the outcomes of the meeting.


Assuntos
Biologia Computacional/métodos , Atenção à Saúde , Genômica , Humanos , Itália , Neoplasias/genética , Medicina de Precisão
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