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1.
Proc Natl Acad Sci U S A ; 117(7): 3678-3686, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32019884

RESUMO

An organism tree of life (organism ToL) is a conceptual and metaphorical tree to capture a simplified narrative of the evolutionary course and kinship among the extant organisms. Such a tree cannot be experimentally validated but may be reconstructed based on characteristics associated with the organisms. Since the whole-genome sequence of an organism is, at present, the most comprehensive descriptor of the organism, a whole-genome sequence-based ToL can be an empirically derivable surrogate for the organism ToL. However, experimentally determining the whole-genome sequences of many diverse organisms was practically impossible until recently. We have constructed three types of ToLs for diversely sampled organisms using the sequences of whole genome, of whole transcriptome, and of whole proteome. Of the three, whole-proteome sequence-based ToL (whole-proteome ToL), constructed by applying information theory-based feature frequency profile method, an "alignment-free" method, gave the most topologically stable ToL. Here, we describe the main features of a whole-proteome ToL for 4,023 species with known complete or almost complete genome sequences on grouping and kinship among the groups at deep evolutionary levels. The ToL reveals 1) all extant organisms of this study can be grouped into 2 "Supergroups," 6 "Major Groups," or 35+ "Groups"; 2) the order of emergence of the "founders" of all of the groups may be assigned on an evolutionary progression scale; 3) all of the founders of the groups have emerged in a "deep burst" at the very beginning period near the root of the ToL-an explosive birth of life's diversity.

2.
Genome Biol ; 20(1): 144, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345254

RESUMO

BACKGROUND: Alignment-free (AF) sequence comparison is attracting persistent interest driven by data-intensive applications. Hence, many AF procedures have been proposed in recent years, but a lack of a clearly defined benchmarking consensus hampers their performance assessment. RESULTS: Here, we present a community resource (http://afproject.org) to establish standards for comparing alignment-free approaches across different areas of sequence-based research. We characterize 74 AF methods available in 24 software tools for five research applications, namely, protein sequence classification, gene tree inference, regulatory element detection, genome-based phylogenetic inference, and reconstruction of species trees under horizontal gene transfer and recombination events. CONCLUSION: The interactive web service allows researchers to explore the performance of alignment-free tools relevant to their data types and analytical goals. It also allows method developers to assess their own algorithms and compare them with current state-of-the-art tools, accelerating the development of new, more accurate AF solutions.


Assuntos
Análise de Sequência , Benchmarking , Transferência Genética Horizontal , Internet , Filogenia , Sequências Reguladoras de Ácido Nucleico , Alinhamento de Sequência , Análise de Sequência de Proteína , Software
3.
Proc Natl Acad Sci U S A ; 114(35): 9391-9396, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28808018

RESUMO

Fungi belong to one of the largest and most diverse kingdoms of living organisms. The evolutionary kinship within a fungal population has so far been inferred mostly from the gene-information-based trees ("gene trees"), constructed commonly based on the degree of differences of proteins or DNA sequences of a small number of highly conserved genes common among the population by a multiple sequence alignment (MSA) method. Since each gene evolves under different evolutionary pressure and time scale, it has been known that one gene tree for a population may differ from other gene trees for the same population depending on the subjective selection of the genes. Within the last decade, a large number of whole-genome sequences of fungi have become publicly available, which represent, at present, the most fundamental and complete information about each fungal organism. This presents an opportunity to infer kinship among fungi using a whole-genome information-based tree ("genome tree"). The method we used allows comparison of whole-genome information without MSA, and is a variation of a computational algorithm developed to find semantic similarities or plagiarism in two books, where we represent whole-genomic information of an organism as a book of words without spaces. The genome tree reveals several significant and notable differences from the gene trees, and these differences invoke new discussions about alternative narratives for the evolution of some of the currently accepted fungal groups.


Assuntos
Fungos/genética , Genoma Fúngico , Filogenia , DNA Fúngico , Proteínas Fúngicas , Proteoma
5.
BMC Cancer ; 16: 627, 2016 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-27519791

RESUMO

BACKGROUND: Circulating cell-free DNA (cfDNA) is emerging as a surrogate sample type for mutation analyses. To improve the clinical utility of cfDNA, we developed a sensitive peptide nucleic acid (PNA)-based method for analyzing EGFR and KRAS mutations in the plasma cfDNA of patients with advanced non-small cell lung cancer (NSCLC). METHODS: Baseline tissue and plasma samples were collected from treatment-naïve advanced NSCLC patients participated in a randomized phase II study, which was registered with ClinicalTrials.gov at Feb. 2009 (NCT01003964). EGFR and KRAS mutations in the plasma cfDNA were analyzed retrospectively using a PNA clamping-assisted fluorescence melting curve analysis. The results were compared with those obtained from tissue analysis performed using the direct sequencing. Exploratory analyses were performed to determine survival predicted by the plasma and tissue mutation status. RESULTS: Mutation analyses in matched tissue and plasma samples were available for 194 patients for EGFR and 135 patients for KRAS. The mutation concordance rates were 82.0 % (95 % confidence interval [CI], 76.5-87.4) for EGFR and 85.9 % (95 % CI, 80.1-91.8) for KRAS. The plasma EGFR mutation test sensitivity and specificity were 66.7 % (95 % CI, 60.0-73.3) and 87.4 % (95 % CI, 82.7-92.1), respectively, and the plasma KRAS mutation test sensitivity and specificity were 50.0 % (95 % CI, 41.6-58.4) and 89.4 % (95 % CI, 84.2-94.6), respectively. The predictive value of the plasma EGFR and KRAS mutation status with respect to survival was comparable with that of the tissue mutation status. CONCLUSIONS: These data suggest that plasma EGFR and KRAS mutations can be analyzed using PNA-based real-time PCR methods and used as an alternative to tumor genotyping for NSCLC patients when tumor tissue is not available.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA/sangue , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
J Clin Microbiol ; 48(9): 3127-31, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20573874

RESUMO

The detection of antiviral-resistant hepatitis B virus (HBV) mutations is important for monitoring the response to treatment and for effective treatment decisions. We have developed an array using peptide nucleic acid (PNA) probes to detect point mutations in HBV associated with antiviral resistance. PNA probes were designed to detect mutations associated with resistance to lamivudine, adefovir, and entecavir. The PNA array assay was sensitive enough to detect 10(2) copies/ml. The PNA array assay was able to detect mutants present in more than 5% of the virus population when the total HBV DNA concentration was greater than 10(4) copies/ml. We analyzed a total of 68 clinical samples by this assay and validated its usefulness by comparing results to those of the sequencing method. The PNA array correctly identified viral mutants and has high concordance (98.3%) with direct sequencing in detecting antiviral-resistant mutations. Our results showed that the PNA array is a rapid, sensitive, and easily applicable assay for the detection of antiviral-resistant mutation in HBV. Thus, the PNA array is a useful and powerful diagnostic tool for the detection of point mutations or polymorphisms.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Ácidos Nucleicos Peptídicos , Mutação Puntual , Adenina/análogos & derivados , Adenina/farmacologia , DNA Viral/genética , Guanina/análogos & derivados , Guanina/farmacologia , Hepatite B/virologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Lamivudina/farmacologia , Testes de Sensibilidade Microbiana/métodos , Mutação de Sentido Incorreto , Organofosfonatos/farmacologia , Sensibilidade e Especificidade
7.
J Microbiol Biotechnol ; 20(2): 287-93, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20208431

RESUMO

Reliable discrimination of single nucleotide mismatch was demonstrated using arrays with peptide nucleic acid (PNA) probes. Newly developed PNA probes immobilization method and hybridization conditions for PNA arrays gave excellent specificity and sensitivity. And we compared the specificity, sensitivity, and stability obtained with the PNA and DNA arrays in discriminating single nucleotide mismatches. PNA arrays had superior perfect match-to-mismatch signal ratios and sensitivities. The relative signal intensities of mismatch PNA probes ranged from 1.6% to 12.1% of the perfect match PNA probes. These results demonstrated that the PNA arrays were 2.0 to 37.3 times more specific and about 10 times more sensitive than DNA arrays. A PNA array showed the same specificity and sensitivity after 12-month storage at room temperature.


Assuntos
Vírus da Hepatite B/genética , Análise em Microsséries/métodos , Ácidos Nucleicos Peptídicos/genética , Polimorfismo de Nucleotídeo Único
8.
J Clin Microbiol ; 47(6): 1785-90, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19369432

RESUMO

We describe a novel array for accurate and reliable genotyping of human papillomavirus (HPV) using peptide nucleic acid (PNA) probes. In order to exploit the superior hybridization properties of PNA with target HPV DNAs, we developed a novel PNA array (PANArray HPV). PANArray HPV enables the detection and genotyping of HPVs using 32 type-specific PNA capture probes for medically important HPVs. All tested HPV types showed highly unique hybridization patterns with type-specific PNA probes. PNA array results showed stable specificities and sensitivities after up to 13 months of storage at room temperature. Also, we demonstrated the superior specificity, sensitivity, and stability of PNA arrays for HPV genotyping. We compared the genotyping results of the PNA array to sequencing with MY09/11 PCR products derived from 72 clinical samples. The results showed excellent agreement between the PNA array and sequencing, except for samples reflecting multiple infections. The results from the PNA array were compared with those of type-specific PCR when discrepant results occurred owing to multiple infections. The results for the PNA array matched those of type-specific PCR in all cases. Newly developed PNA arrays show excellent specificity and sensitivity and long shelf life. Our results suggest that the PNA array represents a reliable alternative to conventional DNA arrays for HPV genotyping, as well as for diagnostics.


Assuntos
Análise em Microsséries/métodos , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Ácidos Nucleicos Peptídicos , Genótipo , Humanos , Papillomaviridae/genética , Ácidos Nucleicos Peptídicos/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Cancer Lett ; 245(1-2): 90-5, 2007 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-16455195

RESUMO

We analyzed the mutation spectrum of BRCA1 and BRCA2 genes in 354 Korean breast cancer patients. Overall, 40 patients carried 25 distinct BRCA1/2 mutations including 12 novel mutations. Seven district mutations were found in multiple unrelated patients, with the BRCA2 c.7480C>T mutation detected in eight unrelated patients, accounting for 50% of the mutations detected in BRCA2. The large number (25/40, 62.5%) of recurrent mutations suggests the possibility of developing a simple screening test for these mutations. The frequency of mutations was related to the number and kinds of risk factors, varying from 10.4 to 25% in the five major risk factor groups. The frequency of BRCA mutations in patients with two or more risk factors was markedly higher than that in patients with one risk factor.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação em Linhagem Germinativa , Estudos de Coortes , Análise Mutacional de DNA/métodos , Feminino , Frequência do Gene , Heterozigoto , Humanos , Coreia (Geográfico) , Fases de Leitura Aberta , Fatores de Risco
10.
Acta Cytol ; 48(2): 229-33, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15085758

RESUMO

BACKGROUND: Warthin's tumor may be associated with false positive diagnoses of malignancy on fine needle aspiration. The most common cause of error is markedly atypical squamous metaplasia mimicking metastatic cystic squamous carcinoma. The common location of Warthin's tumors within periparotid nodes may add to the clinical suspicion of metastasis. We report a case of unilateral, multicentric Warthin's tumor arising in periparotid and intraparotid glands, leading to a strong clinical and cytologic suspicion of malignancy. CASE: A 60-year-old female presented with a 3-month history of several enlarged lymph nodes in the right side of the neck. Fine needle aspiration, performed at the right upper neck lymph node, suggested the possibility of metastatic tumor. On computed tomography and ultrasonography there were 4 nodular lesions in the right retromandibular area and lateral aspect of the neck, 1-1.5 cm in diameter. A thyroid scan revealed diffuse enlargement of the thyroid gland and a nodular lesion in the right lobe. Right thyroid lobectomy and modified radical neck dissection, including right superficial parotidectomy, were performed for evaluation of occult malignancy. Histologically we confirmed that the tumor was a synchronous, multicentric Warthin's tumor arising in the parotid gland and intraparotid and paraparotid lymph nodes. CONCLUSION: Clinicians and pathologists should consider an extraparotid Warthin's tumor in the differential diagnosis of multiple cervical masses.


Assuntos
Adenolinfoma/patologia , Linfonodos/patologia , Neoplasias Primárias Múltiplas/patologia , Glândula Parótida/patologia , Neoplasias Parotídeas/secundário , Adenolinfoma/diagnóstico por imagem , Biópsia por Agulha Fina , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Glândula Parótida/diagnóstico por imagem , Neoplasias Parotídeas/diagnóstico por imagem , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/secundário , Tomografia Computadorizada por Raios X
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