Biomedical subjects

Aleksandr Morgulis

Publications and source records attributed to Aleksandr Morgulis.

3 recordsLinked to original sources

PubMed2006

A fast and symmetric DUST implementation to mask low-complexity DNA sequences.

The DUST module has been used within BLAST for many years to mask low-complexity sequences. In this paper, we present a new implementation of the DUST module that uses the same function to assign a complexity score to a sequence, but uses a different rule by which high-scoring sequences are masked. The new rule masks every nucleotide masked by the old rule and occasionally masks more. The new masking rule corrects two related deficiencies with the old rule. First, the new rule is symmetric with respect to reversing the sequence. Second, the new rule is not context sensitive; the decision to mask a subsequence does not depend on what sequences flank it. The new implementation is at least four times faster than the old on the human genome. We show that both the percentage of additional bases masked and the effect on MegaBLAST outputs are very small.

Genome, Human↗

PubMed2005

WindowMasker: window-based masker for sequenced genomes.

MOTIVATION: Matches to repetitive sequences are usually undesirable in the output of DNA database searches. Repetitive sequences need not be matched to a query, if they can be masked in the database. RepeatMasker/Maskeraid (RM), currently the most widely used software for DNA sequence masking, is slow and requires a library of repetitive template sequences, such as a manually curated RepBase library, that may not exist for newly sequenced genomes. RESULTS: We have developed a software tool called WindowMasker (WM) that identifies and masks highly repetitive DNA sequences in a genome, using only the sequence of the genome itself. WM is orders of magnitude faster than RM because WM uses a few linear-time scans of the genome sequence, rather than local alignment methods that compare each library sequence with each piece of the genome. We validate WM by comparing BLAST outputs from large sets of queries applied to two versions of the same genome, one masked by WM, and the other masked by RM. Even for genomes such as the human genome, where a good RepBase library is available, searching the database as masked with WM yields more matches that are apparently non-repetitive and fewer matches to repetitive sequences. We show that these results hold for transcribed regions as well. WM also performs well on genomes for which much of the sequence was in draft form at the time of the analysis. AVAILABILITY: WM is included in the NCBI C++ toolkit. The source code for the entire toolkit is available at ftp://ftp.ncbi.nih.gov/toolbox/ncbi_tools++/CURRENT/. Once the toolkit source is unpacked, the instructions for building WindowMasker application in the UNIX environment can be found in file src/app/winmasker/README.build. SUPPLEMENTARY INFORMATION: Supplementary data are available at ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/windowmasker/windowmasker_suppl.pdf

Algorithms↗

PubMed2005

Protein database searches using compositionally adjusted substitution matrices.

Almost all protein database search methods use amino acid substitution matrices for scoring, optimizing, and assessing the statistical significance of sequence alignments. Much care and effort has therefore gone into constructing substitution matrices, and the quality of search results can depend strongly upon the choice of the proper matrix. A long-standing problem has been the comparison of sequences with biased amino acid compositions, for which standard substitution matrices are not optimal. To address this problem, we have recently developed a general procedure for transforming a standard matrix into one appropriate for the comparison of two sequences with arbitrary, and possibly differing compositions. Such adjusted matrices yield, on average, improved alignments and alignment scores when applied to the comparison of proteins with markedly biased compositions. Here we review the application of compositionally adjusted matrices and consider whether they may also be applied fruitfully to general purpose protein sequence database searches, in which related sequence pairs do not necessarily have strong compositional biases. Although it is not advisable to apply compositional adjustment indiscriminately, we describe several simple criteria under which invoking such adjustment is on average beneficial. In a typical database search, at least one of these criteria is satisfied by over half the related sequence pairs. Compositional substitution matrix adjustment is now available in NCBI's protein-protein version of blast.

Algorithms↗