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1.
Chem Commun (Camb) ; 55(58): 8466-8469, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31265022

RESUMO

We presented a branch migration based PCR in which a branch migration blocker was introduced to selectively reduce the amplification efficiency of the wild-type target and enrich the mutant-type target. The low-abundance mutations could be enriched and then detected by high resolution melting, Sanger sequencing or fluorescent DNA probe.


Assuntos
Análise Mutacional de DNA/métodos , DNA/análise , DNA/genética , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , Sondas de DNA/química , Sondas de DNA/genética , DNA Polimerase Dirigida por DNA/química , Fluorescência , Corantes Fluorescentes/química , Genes , Humanos , Limite de Detecção , Mutação , Hibridização de Ácido Nucleico
2.
BMC Bioinformatics ; 20(Suppl 11): 276, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167633

RESUMO

BACKGROUND: A crucial task in metagenomic analysis is to annotate the function and taxonomy of the sequencing reads generated from a microbiome sample. In general, the reads can either be assembled into contigs and searched against reference databases, or individually searched without assembly. The first approach may suffer from fragmentary and incomplete assembly, while the second is hampered by the reduced functional signal contained in the short reads. To tackle these issues, we have previously developed GRASP (Guided Reference-based Assembly of Short Peptides), which accepts a reference protein sequence as input and aims to assemble its homologs from a database containing fragmentary protein sequences. In addition to a gene-centric assembly tool, GRASP also serves as a homolog search tool when using the assembled protein sequences as templates to recruit reads. GRASP has significantly improved recall rate (60-80% vs. 30-40%) compared to other homolog search tools such as BLAST. However, GRASP is both time- and space-consuming. Subsequently, we developed GRASPx, which is 30X faster than GRASP. Here, we present a completely redesigned algorithm, GRASP2, for this computational problem. RESULTS: GRASP2 utilizes Burrows-Wheeler Transformation (BWT) and FM-index to perform assembly graph generation, and reduces the search space by employing a fast ungapped alignment strategy as a filter. GRASP2 also explicitly generates candidate paths prior to alignment, which effectively uncouples the iterative access of the assembly graph and alignment matrix. This strategy makes the execution of the program more efficient under current computer architecture, and contributes to GRASP2's speedup. GRASP2 is 8-fold faster than GRASPx (and 250-fold faster than GRASP) and uses 8-fold less memory while maintaining the original high recall rate of GRASP. GRASP2 reaches ~ 80% recall rate compared to that of ~ 40% generated by BLAST, both at a high precision level (> 95%). With such a high performance, GRASP2 is only ~3X slower than BLASTP. CONCLUSION: GRASP2 is a high-performance gene-centric and homolog search tool with significant speedup compared to its predecessors, which makes GRASP2 a useful tool for metagenomics data analysis, GRASP2 is implemented in C++ and is freely available from http://www.sourceforge.net/projects/grasp2 .


Assuntos
Genes , Metagenômica/métodos , Análise de Sequência de DNA/métodos , Homologia de Sequência do Ácido Nucleico , Software , Algoritmos , Organismos Aquáticos/genética , Microbiota/genética , Curva ROC , Fatores de Tempo
3.
BMC Bioinformatics ; 20(Suppl 11): 279, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167638

RESUMO

BACKGROUND: Recent advances in whole-genome sequencing and SNP array technology have led to the generation of a large amount of genotype data. Large volumes of genotype data will require faster and more efficient methods for storing and searching the data. Positional Burrows-Wheeler Transform (PBWT) provides an appropriate data structure for bi-allelic data. With the increasing sample sizes, more multi-allelic sites are expected to be observed. Hence, there is a necessity to handle multi-allelic genotype data. RESULTS: In this paper, we introduce a multi-allelic version of the Positional Burrows-Wheeler Transform (mPBWT) based on the bi-allelic version for compression and searching. The time-complexity for constructing the data structure and searching within a panel containing t-allelic sites increases by a factor of t. CONCLUSION: Considering the small value for the possible alleles t, the time increase for the multi-allelic PBWT will be negligible and comparable to the bi-allelic version of PBWT.


Assuntos
Algoritmos , Alelos , Compressão de Dados , Genes , Haplótipos/genética , Humanos , Fatores de Tempo
4.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 29(Suppl. 2b): 221-221, Jun. 2019.
Artigo em Português | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1010327

RESUMO

INTRODUÇÃO: A Síndrome de Brugada é uma cardiopatia de origem genética (autossômica dominante) que predispõe a arritmias ventriculares que podem ser fatais. É provocada geralmente por uma mutação do gene SCN5A. Tem especial prevalência em indivíduos adultos e do sexo masculino. Também ocorre com mais frequência em indivíduos de origem asiática. Pode provocar morte súbita (através de taquicardia ventricular polimórfica), principalmente em indivíduos em repouso ou durante o sono. Em raras descrições na literatura, há relatos de mutação do gene CACNA1C como causador da síndrome. DESCRIÇÃO: Indivíduo do sexo masculino, nascido em 1954, hipertenso, dislipidêmico, tabagista, histórico familiar rico em morte súbita (mãe, irmãos e tios maternos, todos durante o sono). Encaminhado ao serviço em 2009 para estratificação de risco de morte súbita. Apresentava dor torácica tipo angina. Coronariografia apenas demonstrou lesão de 20% em artéria circunflexa. Eletrocardiograma com padrão típico de Síndrome de Brugada (tipo 1). Submetido a Estudo Eletrofisiológico no mesmo ano, sendo induzida Fibrilação Ventricular com um único extraestímulo em ápice de ventrículo direito. Indicado então implante de Cardioversor Desfibrilador Implantável (CDI). Medicado para doença coronariana, manteve-se assintomático do ponto de vista cardiovascular e permanece desta forma até hoje. Em 2017 obtivemos sua análise genética, evidenciando mutação no gene CACNA1C (que é mais descrita como causadora da síndrome de QT Longo tipo 8 ou Síndrome de Timothy). Sua última avaliação ambulatorial foi em janeiro de 2019, onde se encontrava estável clinicamente, sem registros de terapias do CDI, mantendo eletrocardiograma típico de Síndrome de Brugada. CONCLUSÕES: Descrevemos um caso raro de Síndrome de Brugada causada pela mutação no gene CACNA1C. (AU)


Assuntos
Humanos , Síndrome de Brugada , Genes
5.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 29(Suppl. 2b): 12-12, Jun. 2019.
Artigo em Português | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1008852

RESUMO

INTRODUÇÃO: O diagnóstico molecular da hipercolesterolemia familial (HF) é atribuído principalmente as variantes nos genes LDLR, LDLRAP1, APOB e PCSK9. O objetivo deste estudo foi realizar análise in silico para investigar o impacto de variantes sem descrição na literatura no gene APOB observado em pacientes com HF. MÉTODOS: Foram selecionados 141 indivíduos com diagnóstico clínico de HF. As variantes no gene da APOB foram selecionadas após sequenciamento dos éxons de 61 genes utilizando a plataforma MiSeq (Illumina). Os dados foram analisados nos programas Real Time Analysis, MiSeq Reporter, BaseSpace Sequence Hub e VariantStudio. Para a análise in silico, as sequências molde das moléculas da apoB-100 e o LDLr foram selecionadas por modelagem comparativa considerando o maior grau de identidade. As sequências proteicas foram alinhadas e os modelos 3D foram construídos utilizando os programas SEAVIEW e MODELLER v9.21. O gráfico de Ramachandran do modelo de menor energia apresenta 0,5% de outliers e análise de regiões de desordem, como principal validação. Os resultados das conformações de ancoragem foram analisados no software PyMol 2.1. Os estudos de docking molecular foram realizados para identificar o melhor complexo de conformação usando o servidor web clusPRO. RESULTADOS: Após a análise molecular dos 141 pacientes foram identificadas 7 variantes missenses sem descrição na literatura no gene APOB (c.433C>T, c.2630C>T, c.2950G>A, c.5743G>A, c.7367C>A, c.9880T>C e c.10780T>C). Os estudos de docking das variantes demonstraram uma maior afinidade entre o LDLr e a apoB-100 (c.2630C> T; Pro877Leu) em comparação com a proteína não mutada. A troca dos resíduos permaneceu como propriedade físico-química, e comparando as distâncias de ligação das proteínas não-mutadas (5Å) e mutadas (3,5Å), sugere-se uma maior afinidade do complexo (LDLr-apoB-100) para a leucina, tal fato é afirmado pela análise da região de desordens da apoB-100, onde a posição 877 está em uma região desorganizada e flexível. Esta maior afinidade poderia levar a uma menor dissociação intracelular deste complexo, resultando em uma alta taxa de degradação do LDLr pelas enzimas lisossômicas, levando ao aumento da concentração plasmática de LDLc. Para as outras variantes não houve alterações significativas. CONCLUSÃO: Os resultados sugerem que estudos in silico baseados na ferramenta de docking molecular podem melhorar o conhecimento da contribuição genética no desenvolvimento da doença HF. Além disso, a variante APOB c.2630C> T deve ser avaliada in vitropara validação do mecanismo proposto. (AU)


Assuntos
Genes , Hipercolesterolemia
6.
BMC Bioinformatics ; 20(Suppl 8): 289, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182017

RESUMO

BACKGROUND: Gene selection is one of the critical steps in the course of the classification of microarray data. Since particle swarm optimization has no complicated evolutionary operators and fewer parameters need to be adjusted, it has been used increasingly as an effective technique for gene selection. Since particle swarm optimization is apt to converge to local minima which lead to premature convergence, some particle swarm optimization based gene selection methods may select non-optimal genes with high probability. To select predictive genes with low redundancy as well as not filtering out key genes is still a challenge. RESULTS: To obtain predictive genes with lower redundancy as well as overcome the deficiencies of traditional particle swarm optimization based gene selection methods, a hybrid gene selection method based on gene scoring strategy and improved particle swarm optimization is proposed in this paper. To select the genes highly related to out samples' classes, a gene scoring strategy based on randomization and extreme learning machine is proposed to filter much irrelevant genes. With the third-level gene pool established by multiple filter strategy, an improved particle swarm optimization is proposed to perform gene selection. In the improved particle swarm optimization, to decrease the likelihood of the premature of the swarm the Metropolis criterion of simulated annealing algorithm is introduced to update the particles, and the half of the swarm are reinitialized when the swarm is trapped into local minima. CONCLUSIONS: Combining the gene scoring strategy with the improved particle swarm optimization, the new method could select functional gene subsets which are significantly sensitive to the samples' classes. With the few discriminative genes selected by the proposed method, extreme learning machine and support vector machine classifiers achieve much high prediction accuracy on several public microarray data, which in turn verifies the efficiency and effectiveness of the proposed gene selection method.


Assuntos
Algoritmos , Genes , Bases de Dados Genéticas , Humanos , Aprendizado de Máquina , Neoplasias/genética
7.
BMC Bioinformatics ; 20(Suppl 10): 245, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31138119

RESUMO

BACKGROUND: The selection of reference genes is essential for quantifying gene expression. Theoretically they should be expressed stably and not regulated by experimental or pathological conditions. However, identification and validation of reference genes for human cancer research are still being regarded as a critical point, because cancerous tissues often represent genetic instability and heterogeneity. Recent pan-cancer studies have demonstrated the importance of the appropriate selection of reference genes for use as internal controls for the normalization of gene expression; however, no stably expressed, consensus reference genes valid for a range of different human cancers have yet been identified. RESULTS: In the present study, we used large-scale cancer gene expression datasets from The Cancer Genome Atlas (TCGA) database, which contains 10,028 (9,364 cancerous and 664 normal) samples from 32 different cancer types, to confirm that the expression of the most commonly used reference genes is not consistent across a range of cancer types. Furthermore, we identified 38 novel candidate reference genes for the normalization of gene expression, independent of cancer type. These genes were found to be highly expressed and highly connected to relevant gene networks, and to be enriched in transcription-translation regulation processes. The expression stability of the newly identified reference genes across 29 cancerous and matched normal tissues were validated via quantitative reverse transcription PCR (RT-qPCR). CONCLUSIONS: We reveal that most commonly used reference genes in current cancer studies cannot be appropriate to serve as representative control genes for quantifying cancer-related gene expression levels, and propose in this study three potential reference genes (HNRNPL, PCBP1, and RER1) to be the most stably expressed across various cancerous and normal human tissues.


Assuntos
Pesquisa Biomédica , Regulação Neoplásica da Expressão Gênica , Genes , Neoplasias/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Glicoproteínas de Membrana , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência , Reprodutibilidade dos Testes
8.
BMC Bioinformatics ; 20(1): 268, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138121

RESUMO

BACKGROUND: Correcting a heterogeneous dataset that presents artefacts from several confounders is often an essential bioinformatics task. Attempting to remove these batch effects will result in some biologically meaningful signals being lost. Thus, a central challenge is assessing if the removal of unwanted technical variation harms the biological signal that is of interest to the researcher. RESULTS: We describe a novel framework, B-CeF, to evaluate the effectiveness of batch correction methods and their tendency toward over or under correction. The approach is based on comparing co-expression of adjusted gene-gene pairs to a-priori knowledge of highly confident gene-gene associations based on thousands of unrelated experiments derived from an external reference. Our framework includes three steps: (1) data adjustment with the desired methods (2) calculating gene-gene co-expression measurements for adjusted datasets (3) evaluating the performance of the co-expression measurements against a gold standard. Using the framework, we evaluated five batch correction methods applied to RNA-seq data of six representative tissue datasets derived from the GTEx project. CONCLUSIONS: Our framework enables the evaluation of batch correction methods to better preserve the original biological signal. We show that using a multiple linear regression model to correct for known confounders outperforms factor analysis-based methods that estimate hidden confounders. The code is publicly available as an R package.


Assuntos
Algoritmos , Biologia Computacional/métodos , Bases de Dados Genéticas , Epistasia Genética , Genes , Área Sob a Curva , Regulação da Expressão Gênica , Humanos , Curva ROC , Gordura Subcutânea/metabolismo
9.
Methods Mol Biol ; 1962: 121-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31020557

RESUMO

Gene prediction, also known as gene identification, gene finding, gene recognition, or gene discovery, is among one of the important problems of molecular biology and is receiving increasing attention due to the advent of large-scale genome sequencing projects. We designed an ab initio model (called ChemGenome) for gene prediction in prokaryotic genomes based on physicochemical characteristics of codons. In this chapter, we present the methodology of the latest version of this model ChemGenome2.1 (CG2.1). The first module of the protocol builds a three-dimensional vector from three calculated quantities for each codon-the double-helical trinucleotide base pairing energy, the base pair stacking energy, and an index of the propensity of a codon for protein-nucleic acid interactions. As this three-dimensional vector moves along any genome, the net orientation of the resultant vector should differ significantly for gene and non-genic regions to make a distinction feasible. The predicted putative protein-coding genes from above parameters are passed through a second module of the protocol which reduces the number of false positives by utilizing a filter based on stereochemical properties of protein sequences. The chemical properties of amino acid side chains taken into consideration are the presence of sp3 hybridized γ carbon atom, hydrogen bond donor ability, short/absence of δ carbon and linearity of the side chains/non-occurrence of bi-dentate forks with terminal hydrogen atoms in the side chain. The final prediction of the potential protein-coding genes is based on the frequency of occurrence of amino acids in the predicted protein sequences and their deviation from the frequency values of Swissprot protein sequences, both at monomer and tripeptide levels. The final screening is based on Z-score. Though CG2.1 is a gene finding tool for prokaryotes, considering the underlying similarity in the chemical and physical properties of DNA among prokaryotes and eukaryotes, we attempted to evaluate its applicability for gene finding in the lower eukaryotes. The results give a hope that the concept of gene finding based on physicochemical model of codons is a viable idea for eukaryotes as well, though, undoubtedly, improvements are needed.


Assuntos
Células Eucarióticas/fisiologia , Genes , Genoma , Software , Algoritmos , Códon/química , Internet
10.
Perspect Biol Med ; 62(1): 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031294

RESUMO

New techniques have made genome modification cheaper, easier, and faster, leading to a boom in research, especially for biomedical uses. Given the scope and potential power of this research and its applications, people need accurate information about what is being done or proposed, and why, and what the social and political implications might be. Metaphors can be useful in explaining complex topics, as they present the new in terms of the familiar. However, they can also misrepresent both how genomes and bodies work and the social and political implications of research and applications. Existing research shows that this is happening and that we need new language. However, it is not always easy to decide whether an alternative does rhetorical work that will empower publics, patients, biologists, and physicians alike. This article offers a conceptual framework for developing, analyzing, critiquing, and choosing new metaphors that will help improve communication about genomes and genomic research.


Assuntos
Genômica , Metáfora , Pareamento de Bases , DNA , Interação Gene-Ambiente , Genes , Genoma , Humanos , Proteínas/genética
11.
Perspect Psychol Sci ; 14(3): 376-396, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30844327

RESUMO

Loneliness is a negative and distressing emotional state that arises from a discrepancy between one's desired and achieved levels of social connectedness. The evolutionary theory of loneliness (ETL) posits that experiencing loneliness is an inherited adaptation that signals that salutary social relations are endangered or damaged and prompts people to reconnect to significant others. The basic tenets of the ETL has led researchers to examine the genetic underpinnings of loneliness. The current review provides an updated overview of genetic studies on loneliness and discusses the importance of genetic research for the ETL. The most recent studies suggest that the many genes that contribute to a small degree to differences in loneliness partially overlap with genes that contribute to neuroticism, but not with depression. In addition, the genetic studies discussed in this review show that genes are unlikely to have a direct effect on loneliness. Instead, environmental factors determine in a dynamic fashion how genes that contribute to loneliness are expressed. Future research on epigenetic processes, such as DNA methylation, can further elucidate the dynamic interplay between genes and the environment and how this interplay contributes to loneliness.


Assuntos
Evolução Biológica , Genes , Solidão , Animais , Epigênese Genética , Interação Gene-Ambiente , Humanos , Solidão/psicologia , Modelos Biológicos , Modelos Psicológicos
12.
BMC Bioinformatics ; 20(1): 106, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819107

RESUMO

BACKGROUND: A large fraction of human and mouse autosomal genes are subject to random monoallelic expression (MAE), an epigenetic mechanism characterized by allele-specific gene expression that varies between clonal cell lineages. MAE is highly cell-type specific and mapping it in a large number of cell and tissue types can provide insight into its biological function. Its detection, however, remains challenging. RESULTS: We previously reported that a sequence-independent chromatin signature identifies, with high sensitivity and specificity, genes subject to MAE in multiple tissue types using readily available ChIP-seq data. Here we present an implementation of this method as a user-friendly, open-source software pipeline for monoallelic gene inference from chromatin (MaGIC). The source code for the MaGIC pipeline and the Shiny app is available at https://github.com/gimelbrantlab/magic . CONCLUSION: The pipeline can be used by researchers to map monoallelic expression in a variety of cell types using existing models and to train new models with additional sets of chromatin marks.


Assuntos
Alelos , Cromatina/genética , Genes , Internet , Aprendizado de Máquina , Animais , Humanos , Camundongos , Reprodutibilidade dos Testes , Software
13.
Database (Oxford) ; 20192019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30888410

RESUMO

Genomic data interpretation often requires analyses that move from a gene-by-gene focus to a focus on sets of genes that are associated with biological phenomena such as molecular processes, phenotypes, diseases, drug interactions or environmental conditions. Unique challenges exist in the curation of gene sets beyond the challenges in curation of individual genes. Here we highlight a literature curation workflow whereby gene sets are curated from peer-reviewed published data into GeneWeaver (GW), a data repository and analysis platform. We describe the system features that allow for a flexible yet precise curation procedure. We illustrate the value of curation by gene sets through analysis of independently curated sets that relate to the integrated stress response, showing that sets curated from independent sources all share significant Jaccard similarity. A suite of reproducible analysis tools is provided in GW as services to carry out interactive functional investigation of user-submitted gene sets within the context of over 150 000 gene sets constructed from publicly available resources and published gene lists. A curation interface supports the ability of users to design and maintain curation workflows of gene sets, including assigning, reviewing and releasing gene sets within a curation project context.


Assuntos
Curadoria de Dados , Bases de Dados Genéticas , Genes , Fenômenos Biológicos , Software , Estresse Fisiológico , Fluxo de Trabalho
14.
BMC Bioinformatics ; 20(1): 79, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30767762

RESUMO

BACKGROUND: Functional annotation of genes is an essential step in omics data analysis. Multiple databases and methods are currently available to summarize the functions of sets of genes into higher level representations, such as ontologies and molecular pathways. Annotating results from omics experiments into functional categories is essential not only to understand the underlying regulatory dynamics but also to compare multiple experimental conditions at a higher level of abstraction. Several tools are already available to the community to represent and compare functional profiles of omics experiments. However, when the number of experiments and/or enriched functional terms is high, it becomes difficult to interpret the results even when graphically represented. Therefore, there is currently a need for interactive and user-friendly tools to graphically navigate and further summarize annotations in order to facilitate results interpretation also when the dimensionality is high. RESULTS: We developed an approach that exploits the intrinsic hierarchical structure of several functional annotations to summarize the results obtained through enrichment analyses to higher levels of interpretation and to map gene related information at each summarized level. We built a user-friendly graphical interface that allows to visualize the functional annotations of one or multiple experiments at once. The tool is implemented as a R-Shiny application called FunMappOne and is available at https://github.com/grecolab/FunMappOne . CONCLUSION: FunMappOne is a R-shiny graphical tool that takes in input multiple lists of human or mouse genes, optionally along with their related modification magnitudes, computes the enriched annotations from Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, or Reactome databases, and reports interactive maps of functional terms and pathways organized in rational groups. FunMappOne allows a fast and convenient comparison of multiple experiments and an easy way to interpret results.


Assuntos
Biologia Computacional/métodos , Gráficos por Computador , Bases de Dados Factuais , Ontologia Genética , Genes , Anotação de Sequência Molecular , Software , Animais , Humanos , Camundongos
15.
Mol Phylogenet Evol ; 134: 164-171, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30790674

RESUMO

Fundamental to all phylogenomic studies is the notion that increasing the amount of data - to entire genomes when possible - will increase the accuracy of phylogenetic inference. Simply adding more data does not, however, guarantee phylogenomic inferences will be more accurate. Even genome-scale reconstructions of species histories can suffer the effects of both incomplete lineage sorting (ILS) and gene tree estimation error (GTEE). Weighted statistical binning was originally proposed as a technique to assist the avian phylogenomics project in solving the bird tree of life, which has long eluded resolution as a result of both ILS and GTEE. These so-called "statistical binning procedures" seek to overcome GTEE by concatenating loci into longer multi-locus "supergenes" that are used to reconstruct a species tree under the assumption that the supergene tree set is an accurate estimate of the true underlying gene tree distribution. Here we evaluate the performance of the method using the original avian phylogenomics dataset. Our results suggest that statistical binning constructs false supergenes that concatenate loci with different coalescent histories more often than not: >92% of supergenes comprise discordant loci. Our results underscore a major logical inconsistency: GTEE - the sole justification for using statistical binning instead of standard concatenation - also makes these methods unreliable. These findings underscore the need for developing new robust frameworks for phylogenomic inference that more appropriately accommodate GTEE and ILS at a genome-wide scale.


Assuntos
Genes , Filogenia , Estatística como Assunto , Animais , Aves/genética , Modelos Genéticos , Especificidade da Espécie
16.
Nat Protoc ; 14(3): 703-721, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804569

RESUMO

The PANTHER classification system ( http://www.pantherdb.org ) is a comprehensive system that combines genomes, gene function classifications, pathways and statistical analysis tools to enable biologists to analyze large-scale genome-wide experimental data. The current system (PANTHER v.14.0) covers 131 complete genomes organized into gene families and subfamilies; evolutionary relationships between genes are represented in phylogenetic trees, multiple sequence alignments and statistical models (hidden Markov models (HMMs)). The families and subfamilies are annotated with Gene Ontology (GO) terms, and sequences are assigned to PANTHER pathways. A suite of tools has been built to allow users to browse and query gene functions and analyze large-scale experimental data with a number of statistical tests. PANTHER is widely used by bench scientists, bioinformaticians, computer scientists and systems biologists. Since the protocol for using this tool (v.8.0) was originally published in 2013, there have been substantial improvements and updates in the areas of data quality, data coverage, statistical algorithms and user experience. This Protocol Update provides detailed instructions on how to analyze genome-wide experimental data in the PANTHER classification system.


Assuntos
Genes , Genômica/métodos , Software , Animais , Bases de Dados Genéticas , Ontologia Genética , Genótipo , Humanos , Anotação de Sequência Molecular , Filogenia , Estatística como Assunto
17.
Rev Esp Cardiol (Engl Ed) ; 72(4): 333-340, 2019 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30792015

RESUMO

Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart transplant and has been associated with an increased risk of sudden cardiac death. Risk stratification in these patients continues to be challenging. The identification of the specific etiology of the disease is very useful for the early detection of mutation carriers. Genetic study often provides prognostic information and can determine the therapeutic approach. Wide phenotypic variability is observed depending on the mutated gene, the type of mutation, and the presence of additional genetic and environmental factors.


Assuntos
Cardiomiopatia Dilatada/genética , Testes Genéticos/métodos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas do Citoesqueleto/genética , Desmossomos/genética , Filaminas/genética , Genes , Genes Mitocondriais/genética , Humanos , Proteína 2 de Membrana Associada ao Lisossomo/genética , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Prognóstico , Proteínas de Ligação a RNA/genética , Medição de Risco , Sarcômeros/genética
18.
Biosystems ; 179: 24-29, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30797967

RESUMO

Several algorithms have been proposed for modeling a gene regulatory network from a time-series expression dataset, but these have been used in relatively few studies because experimental cost often restricts the number of sampling time points to less than that of genes by more than one order of magnitude. In order to reduce the number of parameters for network modeling, we propose a method for grouping genes by both temporal expression pattern and biological function, modeling interactions between the gene groups by a dynamic Bayesian network approach. Results from applying the method to a gene expression dataset on human organogenesis demonstrate that more biologically plausible results can be obtained by modeling an interaction network for groups of genes than by modeling that for single genes.


Assuntos
Algoritmos , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Genes , Organogênese , Teorema de Bayes , Embrião de Mamíferos/citologia , Perfilação da Expressão Gênica , Humanos , Modelos Estatísticos , Fatores de Tempo
19.
J Appl Genet ; 60(1): 79-86, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30666567

RESUMO

Among horses selected for speed, the racing line of Quarter Horses is characterized by high performance in sprint races, with these animals being considered the fastest horses in the world. However, few studies have investigated in more detail the polymorphisms and genes that act on this trait. The objective of this study was to analyze exomes and UTRs in regions previously associated with this trait by GWAS in Quarter Horse racehorses with contrasting maximum speed index (SImax), prospecting causal gene polymorphisms that are related to or are in strong linkage disequilibrium with racing performance. Genotypic and phenotypic records from 360 animals of the racing line of Quarter Horses, previously genotyped with an SNP chip to obtain individual genomic estimated breeding values for performance, were used for the formation and sequencing of two groups of animals with contrasting racing performance (20 animals with superior SImax and 20 with inferior SImax). Two rapid runs were performed using two pools of libraries containing 20 and 19 samples randomly chosen among the 40 samples with contrasting SIs. A total of 1203 variants (1105 SNPs and 93 InDels) were identified in 33 regions of interest obtained previously by GWAS. Twenty-nine of the polymorphisms (24 SNPs and 5 InDels) were considered to be important based on three different and independent approaches: SIFT scores classified as deleterious (< 0.05), degree of impact on the consensus region of each polymorphism, and different allele frequencies identified by Fisher's exact test (p < 0.01) between the groups of horses with contrasting SImax. Thus, eight genes described as functional and positional candidates in previous studies (ABCG5, COL11A1, GEN1, SOCS3, MICAL1, SPTBN1, EPB41L3, and SHQ1) and nine new candidate genes (AKNA, ARMC2, FKBP15, LHX1, NOL10, TMEM192, ZFP37, FIG4, and HNRNPU), some of them with known function, were related to racing performance in Quarter Horses.


Assuntos
Genes , Genoma , Cavalos/genética , Polimorfismo de Nucleotídeo Único , Corrida , Esportes , Sequenciamento Completo do Exoma/métodos , Animais
20.
J Appl Genet ; 60(1): 97-101, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30684136

RESUMO

Analysis of allele-specific expression may help to elucidate the genetic architecture of complex traits including fat deposition in pigs. Here, we used pyrosequencing to investigate the allele proportions of candidate genes (ACACA, ADIPOR1, FASN, LEP, ME1, SCD, and TNF) involved in regulation of lipid metabolism in two fat deposits (subcutaneous and visceral fat) and longissimus dorsi muscle of pigs representing Polish Large White, Polish Landrace, Duroc, and Pietrain breeds. We detected differential allelic expression of ACACA, LEP, SCD, and TNF in all tissues analyzed. To search for putative cis-regulatory elements involved in allele-specific expression, we quantified the methylation level within CpG islands located in 5'-flanking regions of ACACA and SCD. Comparison between samples showing markedly disproportionate allelic expression and control groups with similar levels of both alleles did not reveal significant differences. We also assessed the association of rs321308225 (c.*195C>A) an SNP located in the 3'UTR of ACACA with its allelic expression in Polish Landrace pigs, but it was not significant. We conclude that allelic imbalance occurs frequently in regard to genes involved in regulation of lipid deposition in pigs, and further studies are necessary to identify cis-regulatory elements affecting ACACA, LEP, SCD, and TNF expression in porcine fat tissues and skeletal muscle.


Assuntos
Tecido Adiposo/metabolismo , Desequilíbrio Alélico , Genes , Metabolismo dos Lipídeos/genética , Músculo Esquelético/metabolismo , Polimorfismo Genético , Suínos/genética , Acetil-CoA Carboxilase/genética , Alelos , Animais , Leptina/genética , Estearoil-CoA Dessaturase/genética , Fator de Necrose Tumoral alfa/genética
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