Abstract:
:Identifying groups of similar objects is a popular first step in biomedical data analysis, but it is error-prone and impossible to perform manually. Many computational methods have been developed to tackle this problem. Here we assessed 13 well-known methods using 24 data sets ranging from gene expression to protein domains. Performance was judged on the basis of 13 common cluster validity indices. We developed a clustering analysis platform, ClustEval (http://clusteval.mpi-inf.mpg.de), to promote streamlined evaluation, comparison and reproducibility of clustering results in the future. This allowed us to objectively evaluate the performance of all tools on all data sets with up to 1,000 different parameter sets each, resulting in a total of more than 4 million calculated cluster validity indices. We observed that there was no universal best performer, but on the basis of this wide-ranging comparison we were able to develop a short guideline for biomedical clustering tasks. ClustEval allows biomedical researchers to pick the appropriate tool for their data type and allows method developers to compare their tool to the state of the art.
journal_name
Nat Methodsjournal_title
Nature methodsauthors
Wiwie C,Baumbach J,Röttger Rdoi
10.1038/nmeth.3583subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1033-8issue
11eissn
1548-7091issn
1548-7105pii
nmeth.3583journal_volume
12pub_type
杂志文章相关文献
NATURE METHODS文献大全abstract::Drug-inducible systems allowing the control of gene expression in mammalian cells are invaluable tools for genetic research, and could also fulfill essential roles in gene- and cell-based therapy. Currently available systems, however, often have limited in vivo functionality because of leakiness, insufficient levels o...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth846
更新日期:2006-02-01 00:00:00
abstract::Structure probing coupled with high-throughput sequencing could revolutionize our understanding of the role of RNA structure in regulation of gene expression. Despite recent technological advances, intrinsic noise and high sequence coverage requirements greatly limit the applicability of these techniques. Here we desc...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4068
更新日期:2017-01-01 00:00:00
abstract::The ribose of RNA nucleotides can be 2'-O-methylated (Nm). Despite advances in high-throughput detection, the inert chemical nature of Nm still limits sensitivity and precludes mapping in mRNA. We leveraged the differential reactivity of 2'-O-methylated and 2'-hydroxylated nucleosides to periodate oxidation to develop...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4294
更新日期:2017-07-01 00:00:00
abstract::Despite its biological importance, tRNA has not been adequately sequenced by standard methods because of its abundant post-transcriptional modifications and stable structure, which interfere with cDNA synthesis. We achieved efficient and quantitative tRNA sequencing in HEK293T cells by using engineered demethylases to...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3478
更新日期:2015-09-01 00:00:00
abstract::Single-cell transcriptomics provides an opportunity to characterize cell-type-specific transcriptional networks, intercellular signaling pathways and cellular diversity with unprecedented resolution by profiling thousands of cells in a single experiment. However, owing to the unique statistical properties of scRNA-seq...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-019-0372-4
更新日期:2019-05-01 00:00:00
abstract::Single-molecule localization microscopy is a powerful tool for visualizing subcellular structures, interactions and protein functions in biological research. However, inhomogeneous refractive indices inside cells and tissues distort the fluorescent signal emitted from single-molecule probes, which rapidly degrades res...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-020-0816-x
更新日期:2020-05-01 00:00:00
abstract::Traditionally, crystallographic analysis of macromolecules has depended on large, well-ordered crystals, which often require significant effort to obtain. Even sizable crystals sometimes suffer from pathologies that render them inappropriate for high-resolution structure determination. Here we show that fragmentation ...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4178
更新日期:2017-02-13 00:00:00
abstract::We report attainment of subdiffraction resolution using stimulated emission depletion (STED) microscopy with GFP-labeled samples. The approximately 70 nm lateral resolution attained in this study is demonstrated by imaging GFP-labeled viruses and the endoplasmic reticulum (ER) of a mammalian cell. Our results mark the...
journal_title:Nature methods
pub_type: 杂志文章,评审
doi:10.1038/nmeth922
更新日期:2006-09-01 00:00:00
abstract::Determining the structure and composition of macromolecular assemblies is a major challenge in biology. Here we describe ultrastructure expansion microscopy (U-ExM), an extension of expansion microscopy that allows the visualization of preserved ultrastructures by optical microscopy. This method allows for near-native...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-018-0238-1
更新日期:2019-01-01 00:00:00
abstract::Engineering precise genetic changes in a genome is powerful way to study gene function, and several recent papers describe new applications of gene-editing tools. Working with researchers at Sangamo BioSciences, Howard Hughes Medical Institute investigator Barbara Meyer and her colleagues at the University of Californ...
journal_title:Nature methods
pub_type: 评论,杂志文章
doi:10.1038/nmeth.1683
更新日期:2011-09-01 00:00:00
abstract::We present a method to robustly discriminate clustered from randomly distributed molecules detected with techniques based on single-molecule localization microscopy, such as PALM and STORM. The approach is based on deliberate variation of labeling density, such as titration of fluorescent antibody, combined with quant...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3897
更新日期:2016-08-01 00:00:00
abstract::Understanding how chromatin is regulated is essential to fully grasp genome biology, and establishing the locus-specific protein composition is a major step toward this goal. Here we explain why the isolation and analysis of a specific chromatin segment are technically challenging, independently of the method. We then...
journal_title:Nature methods
pub_type: 杂志文章,评审
doi:10.1038/s41592-020-0765-4
更新日期:2020-04-01 00:00:00
abstract::We developed a quantitative PCR method featuring a reusable single-cell cDNA library immobilized on beads for measuring the expression of multiple genes in a single cell. We used this method to analyze multiple cDNA targets (from several copies to several hundred thousand copies) with an experimental error of 15.9% or...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1338
更新日期:2009-07-01 00:00:00
abstract::Microarrays have been widely used for the analysis of gene expression, but the issue of reproducibility across platforms has yet to be fully resolved. To address this apparent problem, we compared gene expression between two microarray platforms: the short oligonucleotide Affymetrix Mouse Genome 430 2.0 GeneChip and a...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth757
更新日期:2005-05-01 00:00:00
abstract::We combined rapid microfluidic mixing with single-molecule fluorescence resonance energy transfer to study the folding kinetics of the intrinsically disordered human protein α-synuclein. The time-resolution of 0.2 ms revealed initial collapse of the unfolded protein induced by binding with lipid mimics and subsequent ...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1568
更新日期:2011-03-01 00:00:00
abstract::We established a conditional site-specific recombination system based on dimerizable Cre recombinase-mediated recombination in the apicomplexan parasite Toxoplasma gondii. Using a new single-vector strategy that allows ligand-dependent, efficient removal of a gene of interest, we generated three knockouts of apicomple...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.2301
更新日期:2013-02-01 00:00:00
abstract::Recent work has demonstrated that environmental factors experienced by parents can affect their offspring across multiple generations, and that such transgenerational transmission can depend on the germline. Causal evidence for the involvement of germ cells is rare, however, and the underlying molecular mechanisms rem...
journal_title:Nature methods
pub_type: 杂志文章,评审
doi:10.1038/nmeth.4181
更新日期:2017-02-28 00:00:00
abstract::We present functional ultrasound (fUS), a method for imaging transient changes in blood volume in the whole brain at better spatiotemporal resolution than with other functional brain imaging modalities. fUS uses plane-wave illumination at high frame rate and can measure blood volumes in smaller vessels than previous u...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1641
更新日期:2011-07-03 00:00:00
abstract::Monomeric (m)Eos2 is an engineered photoactivatable fluorescent protein widely used for super-resolution microscopy. We show that mEos2 forms oligomers at high concentrations and forms aggregates when labeling membrane proteins, limiting its application as a fusion partner. We solved the crystal structure of tetrameri...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.2021
更新日期:2012-05-13 00:00:00
abstract::The complexity of the angiogenic cascade limits cellular approaches to studying angiogenic endothelial cells (ECs). In turn, in vivo assays do not allow the analysis of the distinct cellular behavior of ECs during angiogenesis. Here we show that ECs can be grafted as spheroids into a matrix to give rise to a complex t...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1198
更新日期:2008-05-01 00:00:00
abstract::Epistasis analysis, which reports on the extent to which the function of one gene depends on the presence of a second, is a powerful tool for studying the functional organization of the cell. Systematic genome-wide studies of epistasis, however, have been limited, with the majority of data being collected in the buddi...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth1098
更新日期:2007-10-01 00:00:00
abstract::Protein-RNA networks are ubiquitous and central in biological control. We present an approach termed RNA Tagging that enables the user to identify protein-RNA interactions in vivo by analyzing purified cellular RNA, without protein purification or cross-linking. An RNA-binding protein of interest is fused to an enzyme...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3651
更新日期:2015-12-01 00:00:00
abstract::We describe a general approach for refining protein structure models on the basis of cryo-electron microscopy maps with near-atomic resolution. The method integrates Monte Carlo sampling with local density-guided optimization, Rosetta all-atom refinement and real-space B-factor fitting. In tests on experimental maps o...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3286
更新日期:2015-04-01 00:00:00
abstract::Accurately modeling cellular response to perturbations is a central goal of computational biology. While such modeling has been based on statistical, mechanistic and machine learning models in specific settings, no generalization of predictions to phenomena absent from training data (out-of-sample) has yet been demons...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-019-0494-8
更新日期:2019-08-01 00:00:00
abstract::A 'paired-end ditag' (PET) strategy for pinpointing protein binding sites can reveal a wealth of information about transcription factors and other DNA-binding proteins. ...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth0506-341
更新日期:2006-05-01 00:00:00
abstract::Using a line-scanning method during functional magnetic resonance imaging (fMRI), we obtained high temporal (50-ms) and spatial (50-μm) resolution information along the cortical thickness and showed that the laminar position of fMRI onset coincides with distinct neural inputs in rat somatosensory and motor cortices. T...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.2730
更新日期:2014-01-01 00:00:00
abstract::The reconstruction of neuronal populations, a key step in understanding neural circuits, remains a challenge in the presence of densely packed neurites. Here we achieved automatic reconstruction of neuronal populations by partially mimicking human strategies to separate individual neurons. For populations not resolvab...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3662
更新日期:2016-01-01 00:00:00
abstract::Membrane proteins are largely underrepresented among available atomic-resolution structures. The use of detergents in protein purification procedures hinders the formation of well-ordered crystals for X-ray crystallography and leads to slower molecular tumbling, impeding the application of solution-state NMR. Solid-st...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.2248
更新日期:2012-12-01 00:00:00
abstract::We examined cell cycle-dependent changes in the proteome of human cells by systematically measuring protein dynamics in individual living cells. We used time-lapse microscopy to measure the dynamics of a random subset of 20 nuclear proteins, each tagged with yellow fluorescent protein (YFP) at its endogenous chromosom...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth892
更新日期:2006-07-01 00:00:00
abstract::Zinc-finger nucleases (ZFNs) have enabled highly efficient gene targeting in multiple cell types and organisms. Here we describe methods for using simple ssDNA oligonucleotides in tandem with ZFNs to efficiently produce human cell lines with three distinct genetic outcomes: (i) targeted point mutation, (ii) targeted g...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1653
更新日期:2011-07-17 00:00:00