RESUMO
All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
Assuntos
Genes Neoplásicos/genética , Genoma Humano/genética , Mutação/genética , Neoplasias/genética , Adulto , Linhagem Celular Tumoral , Dano ao DNA/genética , Análise Mutacional de DNA , Reparo do DNA/genética , Dosagem de Genes/genética , Humanos , Perda de Heterozigosidade/genética , Masculino , Melanoma/etiologia , Melanoma/genética , MicroRNAs/genética , Mutagênese Insercional/genética , Neoplasias/etiologia , Polimorfismo de Nucleotídeo Único/genética , Medicina de Precisão , Deleção de Sequência/genética , Raios UltravioletaRESUMO
We present a short overview of the system governing data processing and automatic evaluation of predictions in CASP6, implemented at the Livermore Protein Structure Prediction Center. The system incorporates interrelated facilities for registering participants, collecting prediction targets from crystallographers and NMR spectroscopists and making them available to the CASP6 participants, accepting predictions and providing their preliminary evaluation, and finally, storing and visualizing results. We have automatically evaluated predictions submitted to CASP6 using criteria and methods developed over the successive CASP experiments. Also, we have tested a new evaluation technique based on non-rigid-body type superpositions. Approximately the same number of predictions has been submitted to CASP6 as to all previous CASPs combined, making navigation through and understanding of the data particularly challenging. To facilitate this, we have substantially modernized all data handling procedures, including implementation of a dedicated relational database. An overview of our redesigned website is also presented (http://predictioncenter.org/casp6/).
Assuntos
Biologia Computacional/métodos , Proteínas/química , Proteômica/métodos , Algoritmos , Automação , Cristalografia por Raios X , Internet , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , SoftwareRESUMO
Nowadays, scientists may learn a lot about the organisms studied just by analyzing their genetic material. This requires the development of methods of reading genomes with high accuracy. It has become clear that the knowledge of the changes occurring within a viral genome is indispensable for effective fighting of the pathogen. A good example is SARS-CoV, which was a cause of death of many people and frightened the entire world with its fast and hard to prevent propagation. Rapid development of sequencing methods, like shotgun sequencing or sequencing by hybridization (SBH), gives scientists a good tool for reading genomes. However, since sequencing methods can read fragments of up to 1000 bp only, methods for sequence assembling are required in order to read whole genomes. In this paper a new assembling method, based on graph theoretical approach, is presented. The method was tested on SARS-CoV and the results were compared to the outcome of other widely known methods.
Assuntos
Biologia Computacional/métodos , Genoma Viral , Genômica/métodos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Algoritmos , Sequência de Bases , Dados de Sequência MolecularRESUMO
Recently, 454 Life Sciences Corporation proposed a new biochemical approach to DNA sequencing (the 454 sequencing). It is based on the pyrosequencing protocol. The 454 sequencing aims to give reliable output at a low cost and in a short time. The produced sequences are shorter than reads produced by classical methods. Our paper proposes a new DNA assembly algorithm which deals well with such data and outperforms other assembly algorithms used in practice. The constructed SR-ASM algorithm is a heuristic method based on a graph model, the graph being a modified DNA graph proposed for DNA sequencing by hybridization procedure. Other new features of the assembly algorithm are, among others, temporary compression of input sequences, and a new and fast multiple alignment heuristics taking advantage of the way the output data for the 454 sequencing are presented and coded. The usefulness of the algorithm has been proved in tests on raw data generated during sequencing of the whole 1.84Mbp genome of Prochlorococcus marinus bacteria and also on a part of chromosome 15 of Homo sapiens. The source code of SR-ASM can be downloaded from http://bio.cs.put.poznan.pl/ in the section 'Current research'--> 'DNA Assembly'. Among publicly available assemblers our algorithm appeared to generate the best results, especially in the number of produced contigs and in the lengths of the contigs with high similarity to the genome sequence.