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Biases in the Experimental Annotations of Protein Function and Their Effect on Our Understanding of Protein Function Space
2013
PLoS Computational Biology
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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
2016
FEBS Letters
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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
2017
TIBS -Trends in Biochemical Sciences. Regular ed
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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]
2016
Msphere
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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
2021
Genome Biology
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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
2005
PLoS Computational Biology
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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
2005
PLoS Computational Biology
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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
2020
Genes
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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
2011
Molecular & Cellular Proteomics
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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?
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. ...
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
2012
F1000Research
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(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
2013
F1000Research
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(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
2013
Acta Pharmacologica Sinica
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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]
2016
Msphere
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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
2004
IEEE Signal Processing Magazine
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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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