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In vivo mapping of protein complex organization

2017· article· en· W4389022586 on OpenAlexafffundabout
Anne‐Claude Gingras

Bibliographic record

VenueThe FASEB Journal · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBiotin and Related Studies
Canadian institutionsLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsOrganelleCompartmentalization (fire protection)BiotinylationBiologyCell biologyCompartment (ship)Subcellular localizationProtein subcellular localization predictionCell fractionationComputational biologyCellular compartmentBiochemistryNucleic acidTransport proteinFunction (biology)ChemistryCellCytoplasmMembraneEnzymeGene

Abstract

fetched live from OpenAlex

Compartmentalization is essential for all complex forms of life. In eukaryotic cells, membrane-bound organelles, as well as a multitude of protein- and nucleic acid-rich subcellular structures, maintain boundaries and serve as enrichment zones to promote and regulate protein function. Consistent with the critical importance of these boundaries, alterations in the machinery that mediate protein transport between these compartments has been implicated in a number of diverse diseases. Understanding the composition of each cellular “compartment” (be it a classical organelle or a large protein complex) remains a challenging task. For soluble protein complexes, approaches such as affinity purification other biochemical fractionation coupled to mass spectrometry provides important insight, but this is not the case for detergent-insoluble components. Classically, both microscopy and organellar purifications have been employed for identifying the composition of these structures, but these approaches have limitations, notably in resolution for standard high-throughput fluorescence microscopy and in the difficulty in purifying some of the structures (e.g. p-bodies) for approaches based on biochemical isolations. Prompted by the recent implementation in vivo biotinylation approaches such as BioID, we report here the systematic mapping of the composition of various subcellular structures, using as baits proteins (or protein fragments) which are well-characterized markers for a specified location. We defined how relationships between “prey” proteins detected through this approach can help understanding the protein organization inside a cell. We will discuss our low-resolution map of a human cell containing major organelles and non-membrane bound structures, but also a higher resolution map of RNA-containing cellular structures, including the p-bodies and the stress granules that regulate mRNA stability. This will be presented alongside new computational tools that will help the scientific community to make use of our dataset. Support or Funding Information We acknowledge the support of the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. A draft map of a human cell using proximity biotinylation A draft map of a human cell using proximity biotinylation

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.198

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.251
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2017
Admission routes3
Has abstractyes

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