Improving the sensitivity of the sequence profile method

Lüthy, Roland; Xénarios, Ioannis; Bücher, Philipp

doi:10.1002/pro.5560030118

Cited by 111 publications

(49 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two different types of PSSMs were tested. One was constructed by the average score method (Gribskov et al, 1987;Luthy et al, 1994;Thompson et al, 1994b), and the other by a log-odds method, using position-based substitution-probability A. Sample calculation of counts for column 1 of the alignment in Table 2Aa ny = 0.867 + 0.867 + 1.000 = 2.734 aCalculations for alanine (A) are shown as an example of those for the 18 amino acids that do not occur in this column of the block.…”

Section: Evaluation Of Resultsmentioning

confidence: 99%

Embedding strategies for effective use of information from multiple sequence alignments

Henikoff

1997

Protein Science

View full text Add to dashboard Cite

We describe a new strategy for utilizing multiple sequence alignment information to detect distant relationships in searches of sequence databases. A single sequence representing a protein family is enriched by replacing conserved regions with position-specific scoring matrices (PSSMs) or consensus residues derived from multiple alignments of family members. In comprehensive tests of these and other family representations, PSSM-embedded queries produced the best results overall when used with a special version of the Smith-Waterman searching algorithm. Moreover, embedding consensus residues instead of PSSMs improved performance with readily available single sequence query searching programs, such as BLAST and FASTA. Embedding PSSMs or consensus residues into a representative sequence improves searching performance by extracting multiple alignment information from motif regions while retaining single sequence information where alignment is uncertain.Keywords: consensus sequence; homology searching; multiple sequence alignment; protein blocks; sequence databanks Improvements in the efficiency of large-scale DNA sequencing are leading to rapid increases in the number of databank sequences that lack genetic or biochemical documentation. This is clearly the case for databases of cDNA sequence fragments (Boguski et al., 1993), which are thought to represent the majority of all human protein sequences, and for databases from large genome sequencing projects, such as the sequencing of uncharacterized bacterial genomes (Nowak, 1995). Matching these unknown sequences with sequences of known function is a major goal of genome research. Meanwhile, there remains the traditional goal of detecting homologues to help understand the function of a protein of interest to a biologist. Improved methods for detecting homology in database searches aid in achieving both goals.It is widely assumed that homology detection can be improved by utilizing multiple alignment information. Either a single sequence query is used to search for homologues in a database of multiple sequence alignments (Henikoff & Henikoff, 1991;Attwood & Beck, 1994;Sonnhammer & Kahn, 1994) or patterns (Smith & Smith, 1990;Bairoch, 1992), or an alignment or pattern query is used to search a sequence database (Gribskov et al., 1987;Henikoff et al., 1990;Krogh et al., 1994;Neuwald & Green, 1994;Tatusov et al., 1994;Thompson et al., 1994b (Gribskov et al., 1990; Krogh et ah., 1994;Eddy, 1996). In either case, position-specific scoring matrices (PSSMs) can represent all available information in a multiple sequence alignment, and several improvements in constructing PSSMs have been introduced recently (Brown et al., 1993;Tatusov et al., 1994;Bailey & Gribskov, 1996;Henikoff & Henikoff, 1996;Sjolander et al., 1996). However, there are no comprehensive evaluation studies that demonstrate the superiority of any multiple alignment-based querying method over single sequence querying methods such as BLAST ), FASTA (Pearson, 1990), and Smith-Waterman (Smith & Waterman...

show abstract

Section: Evaluation Of Resultsmentioning

confidence: 99%

Embedding strategies for effective use of information from multiple sequence alignments

Henikoff

1997

Protein Science

View full text Add to dashboard Cite

show abstract

“…Because all biochemical attempts to isolate nSMases from mammalian brain tissues failed to yield a sufficient amount of pure protein, we used an approach based on highly sensitive sequence comparisons. Profile-based sequence database searches offer increased sensitivity, as compared with sequence-based searches, because the query profiles exploit the additional information contained in multiple alignments of related sequences (16,17). The generalized profile method (18), an extension of the original sequence profile method (19), allows the reliable determination of statistical significance (20).…”

Section: Resultsmentioning

confidence: 99%

Cloning and characterization of the mammalian brain-specific, Mg ²⁺ -dependent neutral sphingomyelinase

Hofmann¹,

Tomiuk²,

Wolff³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

287

285

View full text Add to dashboard Cite

The enzymatic breakdown of sphingomyelin by sphingomyelinases is considered the major source of the second messenger ceramide. Studies on the contribution of the various described acidic and neutral sphingomyelinases to the signaling pool of ceramide have been hampered by the lack of molecular data on the neutral sphingomyelinases (nSMases). We recently identified a mammalian nSMase, an integral membrane protein with remote similarity to bacterial sphingomyelinases. However, its ubiquitous expression pattern is in contrast to previous findings that sphingomyelinase activity is found mainly in brain tissues. By using an improved database search method, combined with phylogenetic analysis, we identified a second mammalian nSMase (nSMase2) with predominant expression in the brain. The sphingomyelinase activity of nSMase2 has a neutral pH optimum, depends on Mg 2؉ ions, and is activated by unsaturated fatty acids and phosphatidylserine. Immunofluorescence reveals a neuron-specific punctate perinuclear staining, which colocalizes with a Golgi marker in a number of cell lines. The likely identity of nSMase2 with cca1, a rat protein involved in contact inhibition of 3Y1 fibroblasts, suggests a role for this enzyme in cell cycle arrest. Both mammalian nSMases are members of a superfamily of Mg 2؉ -dependent phosphohydrolases, which also contains nucleases, inositol phosphatases, and bacterial toxins.sequence analysis ͉ generalized profiles ͉ Ccr4 ͉ cytolethal distending toxin ͉ three-dimensional structure

show abstract

“…This method is based on Gribskov's original method 8 with modifications published later. 9,10 The development of a profile for a protein domain logically involves several steps as shown in Figure 2.…”

Section: Construction Of Prosite Profilesmentioning

confidence: 99%

PROSITE: A documented database using patterns and profiles as motif descriptors

Sigrist

Cerutti²,

Hulo³

et al. 2002

Briefings in Bioinformatics

811

547

View full text Add to dashboard Cite

Improving the sensitivity of the sequence profile method

Cited by 111 publications

References 18 publications

Embedding strategies for effective use of information from multiple sequence alignments

Embedding strategies for effective use of information from multiple sequence alignments

Cloning and characterization of the mammalian brain-specific, Mg ²⁺ -dependent neutral sphingomyelinase

PROSITE: A documented database using patterns and profiles as motif descriptors

Contact Info

Product

Resources

About

Improving the sensitivity of the sequence profile method

Cited by 111 publications

References 18 publications

Embedding strategies for effective use of information from multiple sequence alignments

Embedding strategies for effective use of information from multiple sequence alignments

Cloning and characterization of the mammalian brain-specific, Mg 2+ -dependent neutral sphingomyelinase

PROSITE: A documented database using patterns and profiles as motif descriptors

Contact Info

Product

Resources

About

Cloning and characterization of the mammalian brain-specific, Mg ²⁺ -dependent neutral sphingomyelinase