| 1. |
- Altenhoff, Adrian M., et al.
(författare)
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Standardized benchmarking in the quest for orthologs
- 2016
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Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 13:5, s. 425-
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Tidskriftsartikel (refereegranskat)abstract
- Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.
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| 2. |
- Liberles, David A., et al.
(författare)
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The interface of protein structure, protein biophysics, and molecular evolution
- 2012
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 21:6, s. 769-785
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Forskningsöversikt (refereegranskat)abstract
- The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.
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| 3. |
- Viklund, Håkan, 1974-
(författare)
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Formalizing life : Towards an improved understanding of the sequence-structure relationship in alpha-helical transmembrane proteins
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genes coding for alpha-helical transmembrane proteins constitute roughly 25% of the total number of genes in a typical organism. As these proteins are vital parts of many biological processes, an improved understanding of them is important for achieving a better understanding of the mechanisms that constitute life.All proteins consist of an amino acid sequence that fold into a three-dimensional structure in order to perform its biological function. The work presented in this thesis is directed towards improving the understanding of the relationship between sequence and structure for alpha-helical transmembrane proteins. Specifically, five original methods for predicting the topology of alpha-helical transmembrane proteins have been developed: PRO-TMHMM, PRODIV-TMHMM, OCTOPUS, Toppred III and SCAMPI. A general conclusion from these studies is that approaches that use multiple sequence information achive the best prediction accuracy. Further, the properties of reentrant regions have been studied, both with respect to sequence and structure. One result of this study is an improved definition of the topological grammar of transmembrane proteins, which is used in OCTOPUS and shown to further improve topology prediction. Finally, Z-coordinates, an alternative system for representation of topological information for transmembrane proteins that is based on distance to the membrane center has been introduced, and a method for predicting Z-coordinates from amino acid sequence, Z-PRED, has been developed.
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