PRINTS prepares for the new millennium

Attwood, Teresa K.; Flower, Darren R.; Lewis, Alicia; Mabey, J. E.; Morgan, Shant; Scordis, Philip; Selley, Julian N.; Wright, William

doi:10.1093/nar/27.1.220

Cited by 123 publications

(56 citation statements)

References 30 publications

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“…One looks at the pattern of hits amongst different phylogenetic groups (Tatusov et al, 1997). Often these focus on the existence of key motifs and patterns associated with function (Zhang et al, 1998;Bork & Koonin, 1996;Attwood et al, 1999).…”

Section: Sequence-functionmentioning

confidence: 99%

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores

Wilson

Kreychman

Gerstein

2000

Journal of Molecular Biology

341

283

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Measuring in a quantitative, statistical sense the degree to which structural and functional information can be``transferred'' between pairs of related protein sequences at various levels of similarity is an essential prerequisite for robust genome annotation. To this end, we performed pairwise sequence, structure and function comparisons on $30,000 pairs of protein domains with known structure and function. Our domain pairs, which are constructed according to the SCOP fold classi®cation, range in similarity from just sharing a fold, to being nearly identical. Our results show that traditional scores for sequence and structure similarity have the same basic exponential relationship as observed previously, with structural divergence, measured in RMS, being exponentially related to sequence divergence, measured in percent identity. However, as the scale of our survey is much larger than any previous investigations, our results have greater statistical weight and precision. We have been able to express the relationship of sequence and structure similarity using more``modern scores,``such as Smith-Waterman alignment scores and probabilistic P-values for both sequence and structure comparison. These modern scores address some of the problems with traditional scores, such as determining a conserved core and correcting for length dependency; they enable us to phrase the sequence-structure relationship in more precise and accurate terms. We found that the basic exponential sequence-structure relationship is very general: the same essential relationship is found in the different secondary-structure classes and is evident in all the scoring schemes. To relate function to sequence and structure we assigned various levels of functional similarity to the domain pairs, based on a simple functional classi®cation scheme. This scheme was constructed by combining and augmenting annotations in the enzyme and¯y functional classi®cations and comparing subsets of these to the Escherichia coli and yeast classi®cations. We found sigmoidal relationships between similarity in function and sequence, with clear thresholds for different levels of functional conservation. For pairs of domains that share the same fold, precise function appears to be conserved down to $40 % sequence identity, whereas broad functional class is conserved to $25 %. Interestingly, percent identity is more effective at quantifying functional conservation than the more modern scores (e.g. Pvalues). Results of all the pairwise comparisons and our combined functional classi®cation scheme for protein structures can be accessed from a web database at

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Section: Sequence-functionmentioning

confidence: 99%

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores

Wilson

Kreychman

Gerstein

2000

Journal of Molecular Biology

341

283

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“…To date, 1600 fingerprints have been developed, manually annotated and deposited in the PRINTS database (2). Overall, the database is still relatively small, largely because the detailed annotation of entries is extremely time-consuming.…”

Section: Introductionmentioning

confidence: 99%

PRINTS and PRINTS-S shed light on protein ancestry

Attwood

Blythe²,

Flower³

et al. 2002

Nucleic Acids Research

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The PRINTS database houses a collection of protein fingerprints. These may be used to make family and tentative functional assignments for uncharacterised sequences. The September 2001 release (version 32.0) includes 1600 fingerprints, encoding ∼10 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here its use as a source of annotation in the InterPro resource, and the use of its relational cousin, PRINTS-S, to model relationships between families, including those beyond the reach of conventional sequence analysis approaches. The database is accessible for BLAST, fingerprint and text searches at http://www.bioinf.man.ac.uk/ dbbrowser/PRINTS/.

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“…Most of the increase is due to supplementation of the original BLOCKS database, which is based on fami-lies catalogued in PROSITE (Hofmann et al 1999), with protein families documented in other compendiums: PRINTS (Attwood et al 1999), PFAM (Bateman et al 1999), ProDom (Corpet et al 1999), and DOMO (Gracy and Argos 1998). This "BLOCKS+" database (Henikoff et al 1999) was made nonredundant by applying the blocks-vs.-blocks LAMA searching method (Pietrokovski 1996) to eliminate protein families that shared significant sequence similarities.…”

mentioning

confidence: 99%

Drosophila Genomic Sequence Annotation Using the `BLOCKS+` Database

Henikoff

Henikoff²

2000

Genome Res.

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A simple and general homology-based method for gene finding was applied to the 2.9-Mb Drosophila melanogaster Adh region, the target sequence of the Genome Annotation Assessment Project (GASP). Each strand of the entire sequence was used as query of the BLOCKS+ database of conserved regions of proteins. This led to functional assignments for more than one-third of the genes and two-thirds of the transposons. Considering the enormous size of the query, the fact that only two false-positive matches were reported emphasizes the high selectivity of protein family-based methods for gene finding. We used the search results to improve BLOCKS+ by identifying compositionally biased blocks. Our results confirm that protein family databases can be used effectively in automated sequence annotation efforts.Sequence similarity searches for detecting protein relationships have become so popular that one method for doing this is now familiarly described by the verb "to blast." Detecting a hit in a sequence data bank is frequently the best clue as to the function of a gene, so that sequence similarity searching is de rigeur for any genomic annotation effort. A routine annotation strategy is to first arrive at a gene model (Fields and Soderlund 1990), translate it into protein, then use the predicted protein as query of sequence data banks (Pearson and Lipman 1988;Altschul et al. 1990). Most entrants in the GASP (Genome Annotation Assessment Project) study attempted to find accurate gene models, and their success in doing this is the basis for assessment of their performance (Reese et al. 2000a). Some methods used sequence similarity searches of cDNA databases to aid in predicting accurate gene models. Another method (GeneWise) screened gene models against a protein family database. Our method differs in that we dispensed entirely with the gene modeling step, using the full genomic segment to query a protein family database. The rationale is that protein sequence is so rich in information that even this simple approach will be sufficiently sensitive to find the genes and assign functions to them.Our method is nearly a decade old. Using protein queries to search DNA databases translated in all six frames, which was introduced 12 years ago (Henikoff and Wallace 1988;Pearson and Lipman 1988), has since become a standard procedure, especially for searching EST databases (Adams et al. 1991). Alternatively, a DNA query can be translated for searching protein sequence or protein family databases, such as the BLOCKS database (Henikoff and Henikoff 1991). Entries in the BLOCKS database are ungapped multiple alignments of conserved regions of proteins, averaging four BLOCKS per protein family. In a search, detection of multiple BLOCKS representing a family are combined into a hit. In a translated search, BLOCKS are combined into a hit even when they are in different frames on the same strand. Earlier, we reported the detection of a Pseudomonas cepacia regulatory gene (dgdR) and protein family homology for dgdA within a 4-kb genomic segment...

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PRINTS prepares for the new millennium

Cited by 123 publications

References 30 publications

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores

PRINTS and PRINTS-S shed light on protein ancestry

Drosophila Genomic Sequence Annotation Using the `BLOCKS+` Database

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PRINTS prepares for the new millennium

Cited by 123 publications

References 30 publications

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores

Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores

PRINTS and PRINTS-S shed light on protein ancestry

Drosophila Genomic Sequence Annotation Using the BLOCKS+ Database

Contact Info

Product

Resources

About

Drosophila Genomic Sequence Annotation Using the `BLOCKS+` Database