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==Rationale== | ==Rationale== | ||
| - | While there have been efforts to create ontologies and controlled vocabularies to describe the various types of amino acid modifications that can be observed in proteomics, there has been no proposed succinct notation for describing those modifications in their biological context. This document lays out | + | While there have been efforts to create ontologies and controlled vocabularies to describe the various types of amino acid modifications that can be observed in proteomics, there has been no proposed succinct notation for describing those modifications in their biological context. Existing methods of describing protein modifications also tend to be "crisp" (assigning modifications to specific residues) while most measurements are less precise (assigning modifications to protein domains). This document lays out a notation meant to be use to realistically describe the results of proteomics experiments, using a format similar to the Human Genome Variation Society's notation for describing protein amino acid polymorphisms. |
==Simple modifications== | ==Simple modifications== | ||
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:::ACCESSION:pm.Xnn+MODIFICATION | :::ACCESSION:pm.Xnn+MODIFICATION | ||
| - | where "ACCESSION" is the accession number for the protein, "pm." indicates that it is a protein modification, "X" is the single letter symbol for the amino acid residue, "nn" is its ordinal position in | + | where "ACCESSION" is the accession number for the protein, "pm." indicates that it is a protein modification, "X" is the single letter symbol for the amino acid residue, "nn" is its ordinal position in protein co-ordinates, "+MODIFICATION" specifies the change. For example, using the PSI-MS vocabulary for modifications, the notation |
:::ENSP00000339186:pm.T262+Phospho | :::ENSP00000339186:pm.T262+Phospho | ||
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indicates that for protein accession number ENSP00000339186, a measurement shows that the threonine residue number 262 has been modified by the addition of 79.9663 Daltons. | indicates that for protein accession number ENSP00000339186, a measurement shows that the threonine residue number 262 has been modified by the addition of 79.9663 Daltons. | ||
| + | |||
| + | ==Modified domains== | ||
| + | |||
| + | In this case, the specific residue modified cannot be specified from a measurement. It is possible, however, to determine a specific domain in the protein that has been modified. For example, in mass spectrometry-based proteomics it is common to use tryptic peptides to identify modifications and each tryptic peptide is a domain of the original protein. Similarly, alanine-scanning techniques may show similar biological effects of a modification at several closely sited similar residues. | ||
| + | |||
| + | ===Modification within a domain on specific residues=== | ||
| + | |||
| + | The general format for this type of notation is: | ||
| + | |||
| + | :::ACCESSION:pm.(XY)mm-nn+MODIFICATION | ||
| + | |||
| + | where ACCESSION is the protein accession number, the "(XY)" single letter amino acid codes in parenthesis are the specific types of residues that may be modified and "mm-nn" are the start and end of the domain in protein co-ordinates. For example, if a serine/threonine phosphorylation has been traced to the domain "141 SSSTQLR 147" of protein with the Uniprot accession code "up|QRTFRC|", this would be expressed as: | ||
| + | |||
| + | :::up|QRTFRC|:pm.(ST)141-147+Phospho | ||
Contents |
While there have been efforts to create ontologies and controlled vocabularies to describe the various types of amino acid modifications that can be observed in proteomics, there has been no proposed succinct notation for describing those modifications in their biological context. Existing methods of describing protein modifications also tend to be "crisp" (assigning modifications to specific residues) while most measurements are less precise (assigning modifications to protein domains). This document lays out a notation meant to be use to realistically describe the results of proteomics experiments, using a format similar to the Human Genome Variation Society's notation for describing protein amino acid polymorphisms.
The general nomenclature format proposed for the case where the modification is being described as a change to the structure of the amino acid residue in question:
where "ACCESSION" is the accession number for the protein, "pm." indicates that it is a protein modification, "X" is the single letter symbol for the amino acid residue, "nn" is its ordinal position in protein co-ordinates, "+MODIFICATION" specifies the change. For example, using the PSI-MS vocabulary for modifications, the notation
indicates that for the protein accession number ENSP00000339186, the threonine residue number 262 is phosphorylated. It should be noted that the "+" symbol indicates that the side chain has changed: the change may result in either an increase or decrease in residue molecular mass.
Another approach taken to specifying residue modifications is to consider each modified residue to be a completely new amino acid: the PSI-MOD ontology uses this philosophy. If this type of residue replacement idea is to be used, then the notation will be:
where "=NEW_RESIDUE" uses the residue-specification ontology required. Using this strategy for naming the modification in the previous example:
indicates that for protein accession number ENSP00000339186, the threonine residue number 262 has been replaced with the residue specified by the PSI-MOD ID "MOD:00047" (O-phospho-L-threonine).
Some times, when using mass spectrometry based approaches to proteomics, it is not possible (or wise) to attribute a particular measured mass difference to a specific residue modification. In such a case, the appropriate nomenclature would be:
where "#DELTA" is the difference between the measured mass and the residue mass of "X" in Daltons. Using the example above,
indicates that for protein accession number ENSP00000339186, a measurement shows that the threonine residue number 262 has been modified by the addition of 79.9663 Daltons.
In this case, the specific residue modified cannot be specified from a measurement. It is possible, however, to determine a specific domain in the protein that has been modified. For example, in mass spectrometry-based proteomics it is common to use tryptic peptides to identify modifications and each tryptic peptide is a domain of the original protein. Similarly, alanine-scanning techniques may show similar biological effects of a modification at several closely sited similar residues.
The general format for this type of notation is:
where ACCESSION is the protein accession number, the "(XY)" single letter amino acid codes in parenthesis are the specific types of residues that may be modified and "mm-nn" are the start and end of the domain in protein co-ordinates. For example, if a serine/threonine phosphorylation has been traced to the domain "141 SSSTQLR 147" of protein with the Uniprot accession code "up|QRTFRC|", this would be expressed as: