Predicting function: from genes to genomes and back 1 1Edited by P. E. Wright

Bork, Peer; Dandekar, Thomas; Diaz-Lazcoz, Yolande; Eisenhaber, Frank; Huynen, Martijn; Yuan, Yan P.

doi:10.1006/jmbi.1998.2144

Cited by 411 publications

(271 citation statements)

References 137 publications

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“…The classic tool to do so, homology detection, is mainly suited to predict the molecular function of a protein. Because we have complete genome sequences we would also like to know proteins' functions at a higher level [1], for example the pathway or complex a protein belongs to.…”

Section: Introductionmentioning

confidence: 99%

Function prediction and protein networks

Huynen

Snel

Mering

et al. 2003

Current Opinion in Cell Biology

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128

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Section: Introductionmentioning

confidence: 99%

Function prediction and protein networks

Huynen

Snel

Mering

et al. 2003

Current Opinion in Cell Biology

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128

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“…However, many instances of gaps in metabolic pathways have been reported, especially when arbitrary similarity cutoffs were imposed in the database searches. Comparative protein sequence analysis, with the attention to both close and more distant similarities, remains the principal method of function prediction and pathway reconstruction (Tatusov et al 1996;Koonin et al 1997;Bork et al 1998). In the attempt to break through the "similarity barrier", complementary approaches have been proposed, including identification of genes that are physically close, and presumably coordinately regulated, in multiple genomes (Overbeek et al 1999), and the use of phyletic profiles, i.e., the occurrence in some genomes of sets of genes that are missing in others (Tatusov et al 1997;Pellegrini et al 1999).…”

mentioning

confidence: 99%

Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Smit

Mushegian²

2000

Genome Res.

124

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Isoprenoid compounds are ubiquitous in living species and diverse in biological function. Isoprenoid side chains of the membrane lipids are biochemical markers distinguishing archaea from the rest of living forms. The mevalonate pathway of isoprenoid biosynthesis has been defined completely in yeast, while the alternative, deoxy-D-xylulose phosphate synthase pathway is found in many bacteria. In archaea, some enzymes of the mevalonate pathway are found, but the orthologs of three yeast proteins, accounting for the route from phosphomevalonate to geranyl pyrophosphate, are missing, as are the enzymes from the alternative pathway. To understand the evolution of isoprenoid biosynthesis, as well as the mechanism of lipid biosynthesis in archaea, sequence motifs in the known enzymes of the two pathways of isoprenoid biosynthesis were analyzed. New sequence relationships were detected, including similarities between diphosphomevalonate decarboxylase and kinases of the galactokinase superfamily, between the metazoan phosphomevalonate kinase and the nucleoside monophosphate kinase superfamily, and between isopentenyl pyrophosphate isomerases and MutT pyrophosphohydrolases. Based on these findings, orphan members of the galactokinase, nucleoside monophosphate kinase, and pyrophosphohydrolase families in archaeal genomes were evaluated as candidate enzymes for the three missing steps. Alternative methods of finding these missing links were explored, including physical linkage of open reading frames and patterns of ortholog distribution in different species. Combining these approaches resulted in the generation of a short list of 13 candidate genes for the three missing functions in archaea, whose participation in isoprenoid biosynthesis is amenable to biochemical and genetic investigation.

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“…Biological function is an abstract term that can be applied to different scales -from biomolecules via cells to species and large ecosystems [1]. Although biologists are comfortable talking about the concept of function, we often struggle when it comes to quantifying it.…”

Section: Introductionmentioning

confidence: 99%

“…This is partly due to our limited understanding of the underlying biological processes, which prevents us from creating a semantic framework to describe our findings. In addition, a full description of biological function has to take into account both its temporal and its spatial aspects; this has been historically hampered by the lack of adequate data [1]. Today, the most important agents of biological function -proteins -are being catalogued on a variety of scales, from macromolecular complexes at the subcellular level (e.g.…”

Section: Introductionmentioning

confidence: 99%

Protein function space: viewing the limits or limited by our view?

Raes

Harrington

Singh

et al. 2007

Current Opinion in Structural Biology

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| Given that the number of protein functions on earth is finite, the rapid expansion of biological knowledge and the concomitant exponential increase in the number of protein sequences should, at some point, enable the estimation of the limits of protein function space. The functional coverage of protein sequences can be investigated using computational methods, especially given the massive amount of data being generated by large-scale environmental sequencing (metagenomics). In completely sequenced genomes, the fraction of proteins to which at least some functional features can be assigned has recently risen to as much as ~85%. Although this fraction is more uncertain in metagenomics surveys, because of environmental complexities and differences in analysis protocols, our global knowledge of protein functions still appears to be considerable. However, when we consider protein families, continued sequencing seems to yield an ever-increasing number of novel families. Until we reconcile these two views, the limits of protein space will remain obscured.

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Predicting function: from genes to genomes and back 1 1Edited by P. E. Wright

Cited by 411 publications

References 137 publications

Function prediction and protein networks

Function prediction and protein networks

Biosynthesis of Isoprenoids via Mevalonate in Archaea: The Lost Pathway

Protein function space: viewing the limits or limited by our view?

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