Abstract:
:Pinpointing subcellular protein localizations from microscopy images is easy to the trained eye, but challenging to automate. Based on the Human Protein Atlas image collection, we held a competition to identify deep learning solutions to solve this task. Challenges included training on highly imbalanced classes and predicting multiple labels per image. Over 3 months, 2,172 teams participated. Despite convergence on popular networks and training techniques, there was considerable variety among the solutions. Participants applied strategies for modifying neural networks and loss functions, augmenting data and using pretrained networks. The winning models far outperformed our previous effort at multi-label classification of protein localization patterns by ~20%. These models can be used as classifiers to annotate new images, feature extractors to measure pattern similarity or pretrained networks for a wide range of biological applications.
journal_name
Nat Methodsjournal_title
Nature methodsauthors
Ouyang W,Winsnes CF,Hjelmare M,Cesnik AJ,Åkesson L,Xu H,Sullivan DP,Dai S,Lan J,Jinmo P,Galib SM,Henkel C,Hwang K,Poplavskiy D,Tunguz B,Wolfinger RD,Gu Y,Li C,Xie J,Buslov D,Fironov S,Kiselev A,Panchenko D,Cdoi
10.1038/s41592-019-0658-6subject
Has Abstractpub_date
2019-12-01 00:00:00pages
1254-1261issue
12eissn
1548-7091issn
1548-7105pii
10.1038/s41592-019-0658-6journal_volume
16pub_type
杂志文章相关文献
NATURE METHODS文献大全abstract::Gene expression is extensively regulated at the levels of mRNA stability, localization and translation. However, decoding functional RNA-regulatory features remains a limitation to understanding post-transcriptional regulation in vivo. Here, we developed RNA-element selection assay (RESA), a method that selects RNA el...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4121
更新日期:2017-02-01 00:00:00
abstract:: ...
journal_title:Nature methods
pub_type: 评论,杂志文章
doi:10.1038/s41592-019-0315-0
更新日期:2019-02-01 00:00:00
abstract::We have used a mass spectrometry-based proteomic approach to compile an atlas of the thermal stability of 48,000 proteins across 13 species ranging from archaea to humans and covering melting temperatures of 30-90 °C. Protein sequence, composition and size affect thermal stability in prokaryotes and eukaryotic protein...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-020-0801-4
更新日期:2020-05-01 00:00:00
abstract::Despite widespread use of CRISPR, comprehensive data on the frequency and impact of Cas9-mediated off-targets in modified rodents are limited. Here we present deep-sequencing data from 81 genome-editing projects on mouse and rat genomes at 1,423 predicted off-target sites, 32 of which were confirmed, and show that hig...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-018-0011-5
更新日期:2018-07-01 00:00:00
abstract::Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engi...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-019-0586-5
更新日期:2019-11-01 00:00:00
abstract::An outstanding challenge of epigenome-wide association studies (EWASs) performed in complex tissues is the identification of the specific cell type(s) responsible for the observed differential DNA methylation. Here we present a statistical algorithm called CellDMC ( https://github.com/sjczheng/EpiDISH ), which can ide...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-018-0213-x
更新日期:2018-12-01 00:00:00
abstract::Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR-RfxCas13d can effectively discrimin...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-020-01011-4
更新日期:2021-01-01 00:00:00
abstract::MicroRNA depletion by sequestration produces flexible hypomorphs that mimic mutants obtained by microRNA gene targeting. ...
journal_title:Nature methods
pub_type: 评论,杂志文章
doi:10.1038/nmeth1209-873
更新日期:2009-12-01 00:00:00
abstract::Zinc-finger nucleases (ZFNs) drive efficient genome editing by introducing a double-strand break into the targeted gene. Cleavage is induced when two custom-designed ZFNs heterodimerize upon binding DNA to form a catalytically active nuclease complex. The importance of this dimerization event for subsequent cleavage a...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1539
更新日期:2011-01-01 00:00:00
abstract::Accurate identification of cell subsets in complex populations is key to discovering novelty in multidimensional single-cell experiments. We present X-shift (http://web.stanford.edu/~samusik/vortex/), an algorithm that processes data sets using fast k-nearest-neighbor estimation of cell event density and arranges popu...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3863
更新日期:2016-06-01 00:00:00
abstract:: ...
journal_title:Nature methods
pub_type: 评论,杂志文章
doi:10.1038/s41592-018-0283-9
更新日期:2019-01-01 00:00:00
abstract::We describe a simple method for efficiently labeling cell-surface sialic acid-containing glycans on living animal cells. The method uses mild periodate oxidation to generate an aldehyde on sialic acids, followed by aniline-catalyzed oxime ligation with a suitable tag. Aniline catalysis dramatically accelerates oxime l...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1305
更新日期:2009-03-01 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::Single-molecule localization microscopy techniques have proven to be essential tools for quantitatively monitoring biological processes at unprecedented spatial resolution. However, these techniques are very low throughput and are not yet compatible with fully automated, multiparametric cellular assays. This shortcomi...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4486
更新日期:2017-12-01 00:00:00
abstract::We describe a statistical analysis methodology designed to minimize the impact of off-target activities upon large-scale RNA interference (RNAi) screens in mammalian cells. Application of this approach enhances reconfirmation rates and facilitates the experimental validation of new gene activities through the probabil...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth1089
更新日期:2007-10-01 00:00:00
abstract::Bisulfite sequencing measures absolute levels of DNA methylation at single-nucleotide resolution, providing a robust platform for molecular diagnostics. We optimized bisulfite sequencing for genome-scale analysis of clinical samples: here we outline how restriction digestion targets bisulfite sequencing to hotspots of...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1414
更新日期:2010-02-01 00:00:00
abstract::Genetically encoded unnatural amino acids provide powerful strategies for modulating the molecular functions of proteins in mammalian cells. However, this approach has not been coupled to genome-wide measurements, because efficient incorporation of unnatural amino acids is limited to transient expression settings that...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.3701
更新日期:2016-02-01 00:00:00
abstract::Fluorescence microscopy is a powerful quantitative tool for exploring regulatory networks in single cells. However, the number of molecular species that can be measured simultaneously is limited by the spectral overlap between fluorophores. Here we demonstrate a simple but general strategy to drastically increase the ...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.2069
更新日期:2012-06-03 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature methods
pub_type: 已发布勘误
doi:10.1038/s41592-019-0588-3
更新日期:2019-10-01 00:00:00
abstract::Researchers show that to reliably establish protein interaction networks from microarray data it is necessary to measure saturation binding curves for each arrayed protein and its potential binding partners. ...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth1206-966
更新日期:2006-12-01 00:00:00
abstract::Ribonucleoproteins (RNPs) are key regulators of cellular function. We established an efficient approach, crosslinking of segmentally isotope-labeled RNA and tandem mass spectrometry (CLIR-MS/MS), to localize protein-RNA interactions simultaneously at amino acid and nucleotide resolution. The approach was tested on pol...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4235
更新日期:2017-05-01 00:00:00
abstract::Cell signaling, one of key processes in both normal cellular function and disease, is coordinated by numerous interactions between membrane proteins that change in response to stimuli. We present a split ubiquitin-based method for detection of integral membrane protein-protein interactions (PPIs) in human cells, terme...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.2895
更新日期:2014-05-01 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::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::High-resolution optical imaging is critical to understanding brain function. We demonstrate that three-photon microscopy at 1,300-nm excitation enables functional imaging of GCaMP6s-labeled neurons beyond the depth limit of two-photon microscopy. We record spontaneous activity from up to 150 neurons in the hippocampal...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.4183
更新日期:2017-04-01 00:00:00
abstract::We applied pulse-shape analysis (PulSA) to monitor protein localization changes in mammalian cells by flow cytometry. PulSA enabled high-throughput tracking of protein aggregation, translocation from the cytoplasm to the nucleus and trafficking from the plasma membrane to the Golgi as well as stress-granule formation....
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth.1930
更新日期:2012-03-18 00:00:00
abstract::To enhance the repertoire of molecular tools for studying malaria parasite biology, we adapted a ligand-regulatable FKBP protein destabilization domain (ddFKBP) for use in P. falciparum. We destabilized the reporter yellow fluorescent protein (YFP) and the P. falciparum protease falcipain-2 in a ligand-reversible mann...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth1132
更新日期:2007-12-01 00:00:00
abstract::We developed a highly sensitive parallel allele-specific sequencing (PASS) assay to simultaneously analyze a large number of viral genomes and detect minor drug-resistant populations at approximately 0.1-0.01% levels. Using this assay on samples from individuals infected with human immunodeficiency viruses (HIV), we s...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/nmeth995
更新日期:2007-02-01 00:00:00
abstract::Thus far, optical recording of neuronal activity in freely behaving animals has been limited to a thin axial range. We present a head-mounted miniaturized light-field microscope (MiniLFM) capable of capturing neuronal network activity within a volume of 700 × 600 × 360 µm3 at 16 Hz in the hippocampus of freely moving ...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-018-0008-0
更新日期:2018-06-01 00:00:00
abstract::Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to lar...
journal_title:Nature methods
pub_type: 杂志文章
doi:10.1038/s41592-019-0529-1
更新日期:2019-10-01 00:00:00