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Biases in the Experimental Annotations of Protein Function and Their Effect on Our Understanding of Protein Function Space

Alexandra M. Schnoes, David C. Ream, Alexander W. Thorman, Patricia C. Babbitt, Iddo Friedberg, Christine A. Orengo
2013 PLoS Computational Biology  
Knowing that these biases exist and understanding their characteristics and extent is important for database curators, developers of function annotation programs, and anyone who uses protein function annotation  ...  Since each of the dominant articles describes the use of an assay that can find only one function or a small group of functions, this leads to substantial biases in what we know about the function of many  ...  We are especially grateful to Rachael Huntley for careful reading of the manuscript and for providing detailed explanations of annotation provenance and methodology in UniProt. Author Contributions  ... 
doi:10.1371/journal.pcbi.1003063 pmid:23737737 pmcid:PMC3667760 fatcat:dyez23i4n5hxjbh3lctoen3uvi

Protein function in precision medicine: deep understanding with machine learning

Burkhard Rost, Predrag Radivojac, Yana Bromberg
2016 FEBS Letters  
Instead, we need to better understand all parts of the system to define medically relevant causes and effects: how do particular sequence variants affect particular proteins and pathways?  ...  How do these effects, in turn, cause the health or disease-related phenotype?  ...  Databases of experimentally determined protein structures [16, 17] and annotations [18, 19] , are extremely biased, i.e., they are representative of the current state-of-the-art of experimental science  ... 
doi:10.1002/1873-3468.12307 pmid:27423136 pmcid:PMC5937700 fatcat:f7yfs3d5lbcvboroe6ndspfyfq

Proteome-Scale Human Interactomics

Katja Luck, Gloria M. Sheynkman, Ivy Zhang, Marc Vidal
2017 TIBS -Trends in Biochemical Sciences. Regular ed  
towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life.  ...  Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites.  ...  Richardson, and M. Calderwood for helpful discussions, valuable comments and critical reading of the manuscript.  ... 
doi:10.1016/j.tibs.2017.02.006 pmid:28284537 pmcid:PMC5409865 fatcat:4uexon3eeza3tpuvoriezihmyy

Gene Ontology: Pitfalls, Biases, and Remedies [chapter]

Pascale Gaudet, Christophe Dessimoz
2016 Msphere  
A better understanding of the pitfalls and the biases in the GO should help users make the most of this very rich resource.  ...  In this chapter, we discuss some common misinterpretations of the ontology and the annotations.  ...  Acknowledgements We thank Natasha Glover, Rachel Huntley, Suzanna Lewis, Chris Mungall, and Paul Thomas for detailed and helpful feedback on the manuscript.  ... 
doi:10.1007/978-1-4939-3743-1_14 pmid:27812944 fatcat:trsd4agd5ndrdj2om5lvsw4w7m

Roadblock: improved annotations do not necessarily translate into new functional insights

Nicola A. L. Hall, Becky C. Carlyle, Wilfried Haerty, Elizabeth M. Tunbridge
2021 Genome Biology  
The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.  ...  We apologise to the many researchers whose work we are unable to cite due to limitations of space.  ...  The advent of cost-effective high-throughput nucleotide sequencing means that information about the transcriptome is accruing at an exponential rate, rapidly refining our understanding of the diversity  ... 
doi:10.1186/s13059-021-02542-5 pmid:34809684 pmcid:PMC8607653 fatcat:6lvohwomlfd5rnqyfubf7m3squ

Functional Coverage of the Human Genome by Existing Structures, Structural Genomics Targets and Homology Models

Lei Xie, Philip Bourne
2005 PLoS Computational Biology  
The bias in protein structure and function space resulting from experimental limitations and targeting of particular functional classes of proteins by structural biologists has long been recognized, but  ...  coverage of protein structure and function space relative to the human genome.  ...  Acknowledgments This work is supported by the Protein Data Bank through a multiagency grant (NSF DBI 9814284), and PEB is supported in part by a National Institutes of Health grant (GM63208).  ... 
doi:10.1371/journal.pcbi.0010031.eor fatcat:j2vjtv4kmnh6xfx7os37rwmvhu

Functional Coverage of the Human Genome by Existing Structures, Structural Genomics Targets, and Homology Models

Lei Xie, Philip E. Bourne
2005 PLoS Computational Biology  
The bias in protein structure and function space resulting from experimental limitations and targeting of particular functional classes of proteins by structural biologists has long been recognized, but  ...  coverage of protein structure and function space relative to the human genome.  ...  Acknowledgments This work is supported by the Protein Data Bank through a multiagency grant (NSF DBI 9814284), and PEB is supported in part by a National Institutes of Health grant (GM63208).  ... 
doi:10.1371/journal.pcbi.0010031 pmid:16118666 pmcid:PMC1188274 fatcat:ypxuxo5obzekrhn3shwlqu2cau

Automatic Gene Function Prediction in the 2020's

Stavros Makrodimitris, Roeland C. H. J. van Ham, Marcel J. T. Reinders
2020 Genes  
The current rate at which new DNA and protein sequences are being generated is too fast to experimentally discover the functions of those sequences, emphasizing the need for accurate Automatic Function  ...  of Gene Ontology (GO) annotations, and (5) maximally exploit the GO to obtain performance gains.  ...  Conflicts of Interest: The funder provided support in the form of salaries for S.M. and R.C.H.J.v.H., but had no role in the design of the study, in the writing of the manuscript, or in the decision to  ... 
doi:10.3390/genes11111264 pmid:33120976 fatcat:6e3vtjh36fbthj73f25ev42z4i

Categorizing Biases in High-Confidence High-Throughput Protein-Protein Interaction Data Sets

Xueping Yu, Joseph Ivanic, Vesna Memišević, Anders Wallqvist, Jaques Reifman
2011 Molecular & Cellular Proteomics  
1 The abbreviations used are: AP/MS, affinity purification followed by mass spectroscopy; BGS, binary gold standard; IDBOS, interactions detected based on shuffling; MIPS, Munich Information Center for  ...  Protein Sequences; PCA, protein-fragment complementation assay; Y2H, yeast two-hybrid.  ...  Acknowledgments-The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Army or the U.S.  ... 
doi:10.1074/mcp.m111.012500 pmid:21876202 pmcid:PMC3237088 fatcat:isj27hecdvetxhzgqtl36cmjaa

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

Jeroen Raes, Eoghan Donal Harrington, Amoolya Hardev Singh, Peer Bork
2007 Current Opinion in Structural Biology  
| 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.  ...  of space constraints.  ... 
doi:10.1016/j.sbi.2007.05.010 pmid:17574832 fatcat:a5wfhn663vcu5hqwjlyle5o7tq

Progress and challenges in the computational prediction of gene function using networks

Paul Pavlidis, Jesse Gillis
2012 F1000Research  
(as explained in our work 1 ), and furthermore that such effects will have a strong impact on their results.  ...  So how might one mitigate the effect of multifunctional and scarcely informative annotations?  ...  This opinion article deals with the long standing issue of protein function prediction in its broader sense.  ... 
doi:10.12688/f1000research.1-14.v1 pmid:23936626 pmcid:PMC3782350 fatcat:yf4yjwbthbecvdhez36kf372u4

Progress and challenges in the computational prediction of gene function using networks: 2012-2013 update

Paul Pavlidis, Jesse Gillis
2013 F1000Research  
(as explained in our work 1 ), and furthermore that such effects will have a strong impact on their results.  ...  So how might one mitigate the effect of multifunctional and scarcely informative annotations?  ...  This opinion article deals with the long standing issue of protein function prediction in its broader sense.  ... 
doi:10.12688/f1000research.2-230.v1 pmid:24715959 pmcid:PMC3962002 fatcat:zww622btrvcevdzpq6acwrz5sa

Deorphanizing the human transmembrane genome: A landscape of uncharacterized membrane proteins

Joseph J Babcock, Min Li
2013 Acta Pharmacologica Sinica  
This work is supported by grants to Min LI from the National Institutes of Health (MH084691).  ...  Acknowledgements We thank the Min LI laboratory for valuable discussions and Alison NEAL for editorial assistance.  ...  However, one may speculate that such methods could effectively narrow the search space for novel membrane proteins in experimental studies, particularly in cases where a phenotype of interest is not known  ... 
doi:10.1038/aps.2013.142 pmid:24241348 pmcid:PMC3880479 fatcat:lsxnhc644ndgndgaytgkftmmma

Evaluating Computational Gene Ontology Annotations [chapter]

Nives Škunca, Richard J. Roberts, Martin Steffen
2016 Msphere  
Two avenues to understanding gene function are complementary and often overlapping: experimental work and computational prediction.  ...  Second, we discuss solutions that address these issues, for example, targeted selection of new experimental annotations and leveraging the existing experimental annotations.  ...  Open Access charges were funded by the University College London Library, the Swiss Institute of Bioinformatics, the Agassiz Foundation, and the Foundation for the University of Lausanne.  ... 
doi:10.1007/978-1-4939-3743-1_8 pmid:27812938 fatcat:2rz6jdsuizbzxil2hxwlynd2dq

Computational functional genomics

M.P. Liang, O.G. Troyanskaya, A. Laederach, D.L. Brutlag, R.B. Altman
2004 IEEE Signal Processing Magazine  
Computational and experimental researchers need to model effects of changes in the genomic composition of an organism on the organism's fitness and survival.  ...  FEA-TURE and SeqFEATURE provide a way of annotating protein structures with protein function useful for high-throughput annotation of protein function.  ... 
doi:10.1109/msp.2004.1359143 fatcat:qwcypysmffaalknhoi6tri325e
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