Mutiple Motifs

Charles YanSpring 2006

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Mutiple Motifs

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From Single Motif to Multiple Motifs

One single motif is not sufficent to discriminate a protein family. Multiple motifs have stronger discriminating power.

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Multiple Motifs

Protein function prediction using multiple motifs

Each protein family is characterized by a set of motifs (in stead of a single one).

If a protein contain a set of motifs, it probably belong to the family that the set of motifs correspond to.

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PRINTS

PRINTS (http://umber.sbs.man.ac.uk/dbbrowser/PRINTS/ ) is a database of protein fingerprints.

A fingerprint is a group of conserved motifs used to characterize a protein family;

ftp.bioinf.man.ac.uk/pub/prints PRINTS is now maintained at the University of

Manchester PRINTS VERSION 38.0 (16 June, 2005) 1900 FINGERPRINTS, encoding 11,435 single

motifs

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PRINTS Each fingerprint has been defined and iteratively refined

using database SWISS-PROT/TrEMBL composite. Two types of fingerprint are represented in the database,

i.e. they are either simple or composite, depending on their complexity: simple fingerprints are essentially single-motifs; while composite fingerprints encode multiple motifs. The bulk of the database entries are of the latter type because discrimination power is greater for multi-component searches.

Usually the motifs do not overlap, but are separated along a sequence, though they may be contiguous in 3D-space.

Fingerprints can encode protein folds and functionalities more flexibly and powerfully than can single motifs, full diagnostic potency deriving from the mutual context provided by motif neighbors.

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PRINTS

A motif is a conserved element corresponding to a region whose function or structure is known. It is likely to be predictive of any subsequent occurrence of such a structural/functional region in any other protein sequence.

A motif is represented as a conserved alignment of multiple sequence.

A fingerprint is a set of motifs used to predict the occurrence of similar motifs, either in an individual sequence.

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PRINTS

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PRINTS

The starting point is a multiple sequence alignment of a small number of sequences

Once a motif, or set of motifs, has been identified, the conserved regions are excised in the form of local alignments

The motif/s are used to scan against the database Only those sequences that match with all motifs are

regarded as true matches The additional sequence data from the new true set

is then used to generate another set of aligned motifs, and the database is searched again

Until converge

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PRINTS

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PRINTS

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PRINTS

a) General field

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PRINTS

b) Summary fieldA good fingerprint

should exhibit a clear discrimination cut-off, i.e. shows all true positives matching with all n motifs, perhaps some noise, and few or no matches at intermediate positions of the summary table.

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PRINTS

Motif name Iteration number PCODE: the protein

identification codes of the initial sequences

ST: the location of the motifs within those sequences,

INT: and the interval between adjacent motifs. for the first motif, this is simply the distance from the beginning of the sequence to the start of the motif.

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PRINTS

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PRINTS

FPScanSubmitting a PROTEIN sequence find the closest

matching PRINTS fingerprint/s.

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PRINTS

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PRINTS

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PRINTS

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PRINTS

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PRINTS

GRAPHScanA graphical view of the result of a scan of a

fingerprint against a sequence. Matching motifs are highlighted if they score above the threshold % identity

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PRINTS

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PRINTS

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PRINTS

MULScanThis facility allows multiple sequences to be

scanned against the database, Results are returned via email.

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Related Projects

InterPro - Integrated Resources of Proteins Domains and Functional Sites

BLOCKS - BLOCKS db Pfam - Protein families db (HMM derived) [Mirror at St.

Louis (USA)] PRINTS - Protein Motif fingerprint db ProDom - Protein domain db (Automatically generated) PROTOMAP - An automatic hierarchical classification of

Swiss-Prot proteins SBASE - SBASE domain db SMART - Simple Modular Architecture Research Tool TIGRFAMs - TIGR protein families db