Annotating the Human Proteome

The completion of the human genome has shifted the attention from deciphering the sequence to the identification and characterization of the encoded components. The identification and functional annotation of the proteome is here of special interest and starts with the identification of genes and transcripts as a prerequisite of proteome annotation. Gene predictions are very powerful in predicting most of the exons in a genome, but reliable gene structure predictions of both known and novel genes are dependent on existing transcript and protein information. An enormous amount of data already exists on the function of many human proteins, but this is scattered over many resources. Public domain databases are required to manage and collate this information and present it to the user community in both a human and machine readable manner. The completion of the human genome has shifted the attention from deciphering the sequence to the identification and characterization of the encoded components. The identification and functional annotation of the proteome is here of special interest and starts with the identification of genes and transcripts as a prerequisite of proteome annotation. Gene predictions are very powerful in predicting most of the exons in a genome, but reliable gene structure predictions of both known and novel genes are dependent on existing transcript and protein information. An enormous amount of data already exists on the function of many human proteins, but this is scattered over many resources. Public domain databases are required to manage and collate this information and present it to the user community in both a human and machine readable manner. In November 2004, an article was published in Nature by the International Human Genome Sequencing Centre announcing the finishing of the sequencing of the human genome (1.Stein L.D. Human genome: end of the beginning.Nature. 2004; 431: 915-916Google Scholar). The published sequence covered 99% of the euchromatic genome and contained only 341 gaps. This incredible achievement has rightly been hailed as a foundation for biomedical research in the decades ahead but, in practice, is only the first step in a long and complicated path to decipher the complexity of the proteome content of the human cell.To fully understand the workings of the human proteome, scientists must first be able to identify every protein coding region contained within the genome and the amino acid sequence of the proteins that these regions encode. In addition to this basic information, an incredible amount of metadata needs to be assembled. For example, the signals that trigger the expression of these proteins must be identified, the actual protein expression experimentally observed and catalogued. The subsequent duration of gene expression along with the factors can control its eventual repression, the stability of mRNA transcripts and the rates at which they are translated into protein products must also be known and understood. Every potential site of posttranslational modification of the protein should be identified, the conditions under which these modifications are made and their biological significance understood. The biological function of each protein molecule needs to be catalogued along with how this varies according to the cell type in which it is and the within the The significance of the each protein with proteins, and also needs be at both a and functional and in with of the and by the only this information first to be and this is in over the but the information needs to be and in a that it to with an interest in the of this data is already in published and is to with every the potential user is with a should they to information on a gene and this with that to in this domain databases to this information and it to a the user to the how many protein coding genes are present in the human genome has been a that has scientists long the of sequencing In the to be the of human on the of on data and of sequence human many genes in the human Scholar). an the of experimentally in the which from to of to the of gene This is by An of 2004; a that biological information the of in to the of the to sequence the human genome, gene which gene structure protein and 2004; and which a gene structure and structure and 2004; Scholar). gene at the of of The of protein coding genes by has with each and of the the by of the of coding on the of the human genome is also coding from the human genome sequence of transcripts and of these is by the International International The International An for 2004; which was first for the of the human genome the experimentally protein in the sequence The with the protein predictions of and both protein predictions and experimentally by to a of and proteins of sequence are in as their protein are is by the on the of protein and the data is but to the of in proteins from databases and a sequence be identified, are and can be by the in a are as a of data within the a be to the to be of the human to be transcripts from the human genome, with only of by is to be that the of these gene products can be experimentally over the to a of the human it is to be that the of as to both their and to experimentally the predictions are also to a of transcript and protein for the human protein sequence information from a of the of transcripts from many as genome and gene sequencing in addition to data by protein the for a these be into a and with functional and information. 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The published sequence covered 99% of the euchromatic genome and contained only 341 gaps. This incredible achievement has rightly been hailed as a foundation for biomedical research in the decades ahead but, in practice, is only the first step in a long and complicated path to decipher the complexity of the proteome content of the human fully understand the workings of the human proteome, scientists must first be able to identify every protein coding region contained within the genome and the amino acid sequence of the proteins that these regions encode. In addition to this basic information, an incredible amount of metadata needs to be assembled. For example, the signals that trigger the expression of these proteins must be identified, the actual protein expression experimentally observed and catalogued. The subsequent duration of gene expression along with the factors can control its eventual repression, the stability of mRNA transcripts and the rates at which they are translated into protein products must also be known and understood. Every potential site of posttranslational modification of the protein should be identified, the conditions under which these modifications are made and their biological significance understood. The biological function of each protein molecule needs to be catalogued along with how this varies according to the cell type in which it is and the within the The significance of the each protein with proteins, and also needs be at both a and functional and in with of the and by the only this information first to be and this is in over the but the information needs to be and in a that it to with an interest in the of this data is already in published and is to with every the potential user is with a should they to information on a gene and this with that to in this domain databases to this information and it to a the user to the how many protein coding genes are present in the human genome has been a that has scientists long the of sequencing In the to be the of human on the of on data and of sequence human many genes in the human Scholar). an the of experimentally in the which from to of to the of gene This is by An of 2004; a that biological information the of in to the of the to sequence the human genome, gene which gene structure protein and 2004; and which a gene structure and structure and 2004; Scholar). gene at the of of The of protein coding genes by has with each and of the the by of the of coding on the of the human genome is also coding from the human genome sequence of transcripts and of these is by the International International The International An for 2004; which was first for the of the human genome the experimentally protein in the sequence The with the protein predictions of and both protein predictions and experimentally by to a of and proteins of sequence are in as their protein are is by the on the of protein and the data is but to the of in proteins from databases and a sequence be identified, are and can be by the in a are as a of data within the a be to the to be of the human to be transcripts from the human genome, with only of by is to be that the of these gene products can be experimentally over the to a of the human it is to be that the of as to both their and to experimentally the predictions are also to a of transcript and protein for the human how many protein coding genes are present in the human genome has been a that has scientists long the of sequencing In the to be the of human on the of on data and of sequence human many genes in the human Scholar). an the of experimentally in the which from to of to the of gene This is by An of 2004; a that biological information the of in to the of the to sequence the human genome, gene which gene structure protein and 2004; and which a gene structure and structure and 2004; Scholar). gene at the of of The of protein coding genes by has with each and of the the by of the of coding on the of the human genome is also coding from the human genome sequence of transcripts and Scholar). of these is by the International International The International An for 2004; which was first for the of the human genome the experimentally protein in the sequence The with the protein predictions of and both protein predictions and experimentally by to a of and proteins of sequence are in as their protein are is by the on the of protein and the data is but to the of in proteins from databases and a sequence be identified, are and can be by the in a are as a of data within the a be to the to be of the human to be transcripts from the human genome, with only of by is to be that the of these gene products can be experimentally over the to a of the human it is to be that the of as to both their and to experimentally the predictions are The also to a of transcript and protein for the human protein sequence information from a of the of transcripts from many as genome and gene sequencing in addition to data by protein the for a these be into a and with functional and information. 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