The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.
A number of different approaches have been described to identify proteins from tandem mass spectrometry (MS/MS) data. The most common approaches rely on the available databases to match experimental MS/MS data. These methods suffer from several drawbacks and cannot be used for the identification of proteins from unknown genomes. In this communication, we describe a new de novo sequencing software package, PEAKS, to extract amino acid sequence information without the use of databases. PEAKS uses a new model and a new algorithm to efficiently compute the best peptide sequences whose fragment ions can best interpret the peaks in the MS/MS spectrum. The output of the software gives amino acid sequences with confidence scores for the entire sequences, as well as an additional novel positional scoring scheme for portions of the sequences. The performance of PEAKS is compared with Lutefisk, a well-known de novo sequencing software, using quadrupole-time-of-flight (Q-TOF) data obtained for several tryptic peptides from standard proteins.
Many software tools have been developed for the automated identification of peptides from tandem mass spectra. The accuracy and sensitivity of the identification software via database search are critical for successful proteomics experiments. A new database search tool, PEAKS DB, has been developed by incorporating the de novo sequencing results into the database search. PEAKS DB achieves significantly improved accuracy and sensitivity over two other commonly used software packages. Additionally, a new result validation method, decoy fusion, has been introduced to solve the issue of overconfidence that exists in the conventional target decoy method for certain types of peptide identification software.
PatternHunter is available at http://www.bioinformaticssolutions.com, as a commercial package. It runs on all platforms that support Java. PatternHunter technology is being patented; commercial use requires a license from BSI, while non-commercial use will be free.
A new class of distances appropriate for measuring similarity relations between sequences, say one type of similarity per distance, is studied. We propose a new "normalized information distance", based on the noncomputable notion of Kolmogorov complexity, and show that it is in this class and it minorizes every computable distance in the class (that is, it is universal in that it discovers all computable similarities). We demonstrate that it is a metric and call it the similarity metric. This theory forms the foundation for a new practical tool. To evidence generality and robustness we give two distinctive applications in widely divergent areas using standard compression programs like gzip and GenCompress. First, we compare whole mitochondrial genomes and infer their evolutionary history. This results in a first completely automatic computed whole mitochondrial phylogeny tree. Secondly, we fully automatically compute the language tree of 52 different languages.
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