Detection of distant evolutionary relationships between protein families using theory of sequence profile-profile comparison

<p>Abstract</p> <p>Background</p> <p>Detection of common evolutionary origin (homology) is a primary means of inferring protein structure and function. At present, comparison of protein families represented as sequence profiles is arguably the most effective homology detection strategy. However, finding the best way to represent evolutionary information of a protein sequence family in the profile, to compare profiles and to estimate the biological significance of such comparisons, remains an active area of research.</p> <p>Results</p> <p>Here, we present a new homology detection method based on sequence profile-profile comparison. The method has a number of new features including position-dependent gap penalties and a global score system. Position-dependent gap penalties provide a more biologically relevant way to represent and align protein families as sequence profiles. The global score system enables an analytical solution of the statistical parameters needed to estimate the statistical significance of profile-profile similarities. The new method, together with other state-of-the-art profile-based methods (HHsearch, COMPASS and PSI-BLAST), is benchmarked in all-against-all comparison of a challenging set of SCOP domains that share at most 20% sequence identity. For benchmarking, we use a reference ("gold standard") free model-based evaluation framework. Evaluation results show that at the level of protein domains our method compares favorably to all other tested methods. We also provide examples of the new method outperforming structure-based similarity detection and alignment. The implementation of the new method both as a standalone software package and as a web server is available at <url>http://www.ibt.lt/bioinformatics/coma</url>.</p> <p>Conclusion</p> <p>Due to a number of developments, the new profile-profile comparison method shows an improved ability to match distantly related protein domains. Therefore, the method should be useful for annotation and homology modeling of uncharacterized proteins.</p

A Path to Alignment: Connecting K-12 and Higher Education via the Common Core and the Degree Qualifications Profile

The Common Core State Standards (CCSS), which aim to assure competency in English/language arts and mathematics through the K-12 curriculum, define necessary but not sufficient preparedness for success in college. The Degree Qualifications Profile (DQP), which describes what a college degree should signify, regardless of major, offers useful but not sufficient guidance to high school students preparing for college study. A coordinated strategy to prepare students to succeed in college would align these two undertakings and thus bridge an unfortunate and harmful cultural chasm between the K-12 world and that of higher education. Chasms call for bridges, and the bridge proposed by this white paper could create a vital thoroughfare. The white paper begins with a description of the CCSS and an assessment of their significance. A following analysis then explains why the CCSS, while necessary, are not sufficient as a platform for college success. A corresponding explanation of the DQP clarifies the prompts that led to its development, describes its structure, and offers some guidance for interpreting the outcomes that it defines. Again, a following analysis considers the potential of the DQP and the limitations that must be addressed if that potential is to be more fully realized. The heart of the white paper lies in sections 5 and 6, which provide a crosswalk between the CCSS and the DQP. These sections show how alignments and differences between the two may point to a comprehensive preparedness strategy. They also offer a proposal for a multifaceted strategy to realize the potential synergy of the CCSS and the DQP for the benefit of high school and college educators and their students -- and the nation

Making the Most of Interim Assessment Data: Lessons from Philadelphia

Under No Child Left Behind, urban school districts have increasingly turned to interim assessments, administered at regular intervals, to help gauge student progress in advance of annual state exams. These assessments have spawned growing debate among educators, assessment experts, and the testing industry: are they worth the significant investment of money and time? In Making the Most of Interim Assessment Data: Lessons from Philadelphia, Research for Action (RFA) weighs in on this issue. The School District of Philadelphia (SDP) was an early adopter of interim assessments, implementing the exams in 2003. Unlike teachers in some other regions, Philadelphia elementary and middle grades teachers rated these 'Benchmark' assessments highly. However, the study found that enthusiasm did not necessarily correlate with higher rates of student achievement. What did predict student success were three factors -- instructional leadership, collective responsibility, and use of the SDP's Core Curriculum. The report underscores the value of investment in ongoing data interpretation that emphasizes teachers' learning within formal instructional communities, such as grade groups of teachers. This research was funded by the Spencer Foundation and the William Penn Foundation

Genome-wide detection and analysis of homologous recombination among sequenced strains of Escherichia coli

BACKGROUND: Comparisons of complete bacterial genomes reveal evidence of lateral transfer of DNA across otherwise clonally diverging lineages. Some lateral transfer events result in acquisition of novel genomic segments and are easily detected through genome comparison. Other more subtle lateral transfers involve homologous recombination events that result in substitution of alleles within conserved genomic regions. This type of event is observed infrequently among distantly related organisms. It is reported to be more common within species, but the frequency has been difficult to quantify since the sequences under comparison tend to have relatively few polymorphic sites. RESULTS: Here we report a genome-wide assessment of homologous recombination among a collection of six complete Escherichia coli and Shigella flexneri genome sequences. We construct a whole-genome multiple alignment and identify clusters of polymorphic sites that exhibit atypical patterns of nucleotide substitution using a random walk-based method. The analysis reveals one large segment (approximately 100 kb) and 186 smaller clusters of single base pair differences that suggest lateral exchange between lineages. These clusters include portions of 10% of the 3,100 genes conserved in six genomes. Statistical analysis of the functional roles of these genes reveals that several classes of genes are over-represented, including those involved in recombination, transport and motility. CONCLUSION: We demonstrate that intraspecific recombination in E. coli is much more common than previously appreciated and may show a bias for certain types of genes. The described method provides high-specificity, conservative inference of past recombination events

Local sequence alignments statistics: deviations from Gumbel statistics in the rare-event tail

<p>Abstract</p> <p>Background</p> <p>The optimal score for ungapped local alignments of infinitely long random sequences is known to follow a Gumbel extreme value distribution. Less is known about the important case, where gaps are allowed. For this case, the distribution is only known empirically in the high-probability region, which is biologically less relevant.</p> <p>Results</p> <p>We provide a method to obtain numerically the biologically relevant rare-event tail of the distribution. The method, which has been outlined in an earlier work, is based on generating the sequences with a parametrized probability distribution, which is biased with respect to the original biological one, in the framework of Metropolis Coupled Markov Chain Monte Carlo. Here, we first present the approach in detail and evaluate the convergence of the algorithm by considering a simple test case. In the earlier work, the method was just applied to one single example case. Therefore, we consider here a large set of parameters:</p> <p>We study the distributions for protein alignment with different substitution matrices (BLOSUM62 and PAM250) and affine gap costs with different parameter values. In the logarithmic phase (large gap costs) it was previously assumed that the Gumbel form still holds, hence the Gumbel distribution is usually used when evaluating p-values in databases. Here we show that for all cases, provided that the sequences are not too long (<it>L </it>> 400), a "modified" Gumbel distribution, i.e. a Gumbel distribution with an additional Gaussian factor is suitable to describe the data. We also provide a "scaling analysis" of the parameters used in the modified Gumbel distribution. Furthermore, via a comparison with BLAST parameters, we show that significance estimations change considerably when using the true distributions as presented here. Finally, we study also the distribution of the sum statistics of the <it>k </it>best alignments.</p> <p>Conclusion</p> <p>Our results show that the statistics of gapped and ungapped local alignments deviates significantly from Gumbel in the rare-event tail. We provide a Gaussian correction to the distribution and an analysis of its scaling behavior for several different scoring parameter sets, which are commonly used to search protein data bases. The case of sum statistics of <it>k </it>best alignments is included.</p

Study of flight management requirements during SST low visibility approach and landing operations Final summary report

Flight management operational problems and task requirements for low visibility approach and landing of supersonic transport