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Genome coverage, literally speaking. The challenge of annotating 200 genomes with 4 million publications.

In late 2004, 200 complete genomes had been sequenced and made available to the research community. At the time of writing this viewpoint, that number had further risen to 221 and will have undoubtedly increased again before publication. These genomes, which represent a wide range of species from archaea to human, are a highly valuable knowledge resource for the scientific community. However, the sequencing of a full genome is just the first step in research; it must be followed by the functional characterization of genes and proteins. In this context, it is interesting to see how well represented these sequenced species are in terms of publications. We have thus obtained the number of abstracts published per species and normalized that count by the number of genes in that species to obtain a comparable measure for the number of publications per gene for all completed and published genomes. This simple measure highlights the current knowledge gap between various organisms and could further serve as a guideline for selecting genomes for sequencing projects, high-throughput functional genomics and database annotation efforts. The 200 complete genome sequences published by December 2004 included 118 genera, 166 species and 34 additional strains for 21 species. This rate translates to a doubling time of available genome sequences of less than two years (Janssen et al, 2003a). And it remains steady: in 2003, an average of one complete genome was released per week; 47 genomes were made available in the first 44 weeks of 2004. This trend will accelerate further, as more than 1,000 genome projects are currently underway (Bernal et al, 2001). For the 221 genomes currently available, the total number of predicted proteins is 822,114, according to the COGENT database (Janssen et al, 2003b). One of the great challenges for computational and experimental genomics is the functional characterization of the genes and proteins encoded in these genomes (Eisenberg et al, 2000), a process that should be considered as continuous (Ouzounis & Karp, 2002). To achieve this goal, it is important to rely on existing knowledge and draw from previous studies conducted on these organisms. We have analysed how well each of the currently available genomes is characterized in terms of the number of publications pertinent to the corresponding species. To achieve a reliable measure for the available knowledge per genome, we obtained the number of abstracts per species—but not strain—from Medline and divided this number by the number of predicted protein-encoding genes. The corresponding ratio, which we term the Species Knowledge Index (SKI), thus reflects our current understanding of each of these species. More detailed information on the literature coverage of sequenced organisms, tracked by COGENT, is available through our GenMed server (http://cgg.ebi.ac.uk/cgi-bin/genmed/ genmed.pl). This analysis encompasses 3,806,293 Medline abstracts corresponding to 200 genomes. On average, there are 5 abstracts per gene for the first 200 genomes in the COGENT database, ranging from 1 abstract per 1000 genes for poorly characterized species, to 55.1 abstracts per gene for Escherichia coli (Fig 1A). This arithmetic mean value is grossly distorted by a few outliers (Fig 1B; colour-coded), namely E. coli, human (48.5), Staphylococcus aureus strains (ca. 16-17), mouse (15.6), Helicobacter pylori strains (ca. 13) and Saccharomyces cerevisiae (10.6). If these outliers are excluded, then the average SKI value drops to 0.9 (580,016 abstracts for 651,183 genes). Yet, this value is still dominated either by important pathogens, such as Chlamydia trachomatis (9.5) and Haemophilus influenzae (8.9), or by model organisms such as Pseudomonas aeruginosa (5.7) and Bacillus subtilis (4.8).