CUPID: Core and Unique Protein IDentification
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CUPID: Core and Unique Protein IDentification. Raja Mazumder and Darren A Natale & Protein Information Resource, 3300 Whitehaven St., Georgetown University, Washington, DC 20007. Computational identification of strain-, species- and genus-specific proteins.

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Strain-, species-, and genus-specific core unique proteins from selected organisms

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CUPID: Core and Unique Protein IDentification

Raja Mazumder and Darren A Natale & Protein Information Resource, 3300 Whitehaven St., Georgetown University, Washington, DC 20007

Computational identification of strain-, species- and genus-specific proteins

The identification of unique proteins at different taxonomic levels has both scientific and practical value. Strain-, species- and genus-specific proteins can provide insight into the criteria that define an organism and its relationships with close relatives. Such proteins can also serve as taxon-specific diagnostic targets. We developed a general protocol to identify proteins unique to different taxa, and applied it to a set of food- and water-borne pathogens. Specifically, we: a) identify proteins that are unique to a particular strain, species, or genus; b) extract the set of proteins common to two or more strains or species; and c) determine the organism most closely related to a particular genus, species or strain.

A pipeline using a combination of computational and manual analyses of BLAST results was developed to identify strain-, species-, and genus-specific proteins and to catalog the closest sequenced relative for each protein in a proteome. A flow chart of the method used to detect strain-, species-, or genus-specific proteins is shown here. Proteins were designated as not unique if (a) the protein is part of a merged entry (containing identical proteins from different organisms) and one of the source organisms is considered non-self; (b) the query protein hits a non-self subject with E < 0.001; (c) the non-self best hit, when itself used as a query (in a reverse BLAST), retrieves the initial query as an organism-specific best hit (that is, they are reciprocal best hits, and thus potential orthologs); and (d) the non-self best hit fails to retrieve the initial query as its potential ortholog — but does indeed retrieve the initial query — and manual inspection reveals homology. Sequences that could not retrieve themselves with an expect value of 1e-14 or better in the forward BLAST using the BLOSUM62 matrix were retested using the PAM30 matrix.

Organism

Unique

Virulence

External

Phage

Unknown

Misc.

Helicobacter hepaticus ATCC 51449

253

13

6

18

171

45

Helicobacter pylori 26695

199

9

16

5

159

10

Helicobacter pylori J99

663

11

1

2

637

12

Escherichia coli K12

262

0

8

0

254

0

Escherichia coli O157:H7

259

9

19

8

213

10

Salmonella enterica subsp. enterica serovar Typhi Ty2

244

19

24

0

198

3

Salmonella typhimurium LT2

233

0

2

43

181

7

Summary of annotations for genus-specific unique proteins from selected water- and wastewater-borne pathogens and pathogen-related organisms.

Discussion:

The salient features of CUPID are: a) provides sets of proteins unique to a strain, species, and genus; b) includes a check for additional homologs based on reciprocal hits; c) uses different parameters for short sequences; d) provides the identity of the nearest non-self neighbor; and e) allows retrieval of unique, core, and core unique proteins at different taxonomic levels. One use of the CUPID system is to help identify diagnostic targets specific to a particular clade of these pathogens. The unique proteins form a short list of diagnostic targets which can be validated in the laboratory. A summary of the annotations show that many of the proteins are not annotated. A significant number of the ones that are annotated are related to virulence and/or are external proteins. Proteins predicted to be external to the bacterial cell – possibly involved in host interactions and virulence – may be used to develop protein-based detection systems. In addition, it should be possible to use the DNA encoding these proteins as the basis for diagnostics. However, it is important to note that protein-identified DNA probes must be verified as to their uniqueness at the DNA level.

Example output from CUPID

Organism

Strain-specific proteins

Species-specific proteins

Genus-specific proteins

Helicobacter pylori 26695

53

110

15

Helicobacter pylori J99

17

107

11

Escherichia coli K12

35

15

15

Escherichia coli O157:H7

117

12

12

Acknowledgements: Development of CUPID was supported by grant AWD4220707 from the District of Columbia Water and Sewer Authority. The bioinformatics infrastructure on which CUPID is based was supported in part by grant U01-HG02712 from the National Institutes of Health. This work is described in: Mazumder R, Natale DA, Murthy S, Thiagarajan R, Wu CH. Computational identification of strain-, species- and genus-specific proteins. BMC Bioinformatics. 2005 Nov 23;6:279.

Strain-, species-, and genus-specific core unique proteins from selected organisms

Contact

[email protected]

http://pir.georgetown.edu/cupid


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