Dataset Information

PyBEL: a computational framework for Biological Expression Language.

ABSTRACT: Summary:Biological Expression Language (BEL) assembles knowledge networks from biological relations across multiple modes and scales. Here, we present PyBEL; a software package for parsing, validating, converting, storing, querying, and visualizing networks encoded in BEL. Availability and implementation:PyBEL is implemented in platform-independent, universal Python code. Its source is distributed under the Apache 2.0 License at https://github.com/pybel. Contact:charles.hoyt@scai.fraunhofer.de. Supplementary information:Supplementary data are available at Bioinformatics online.

SUBMITTER: Hoyt CT

PROVIDER: S-EPMC5860616 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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PyBEL: a computational framework for Biological Expression Language.

Hoyt Charles Tapley CT Konotopez Andrej A Ebeling Christian C Wren Jonathan J

Bioinformatics (Oxford, England) 20180201 4

<h4>Summary</h4>Biological Expression Language (BEL) assembles knowledge networks from biological relations across multiple modes and scales. Here, we present PyBEL; a software package for parsing, validating, converting, storing, querying, and visualizing networks encoded in BEL.<h4>Availability and implementation</h4>PyBEL is implemented in platform-independent, universal Python code. Its source is distributed under the Apache 2.0 License at https://github.com/pybel.<h4>Contact</h4>charles.hoy ...[more]

PMID: 29048466

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Project description:Stochastic fluctuations in gene expression give rise to distributions of protein levels across cell populations. Despite a mounting number of theoretical models explaining stochasticity in protein expression, we lack a robust, efficient, assumption-free approach for inferring the molecular mechanisms that underlie the shape of protein distributions. Here we propose a method for inferring sets of biochemical rate constants that govern chromatin modification, transcription, translation, and RNA and protein degradation from stochasticity in protein expression. We asked whether the rates of these underlying processes can be estimated accurately from protein expression distributions, in the absence of any limiting assumptions. To do this, we (1) derived analytical solutions for the first four moments of the protein distribution, (2) found that these four moments completely capture the shape of protein distributions, and (3) developed an efficient algorithm for inferring gene expression rate constants from the moments of protein distributions. Using this algorithm we find that most protein distributions are consistent with a large number of different biochemical rate constant sets. Despite this degeneracy, the solution space of rate constants almost always informs on underlying mechanism. For example, we distinguish between regimes where transcriptional bursting occurs from regimes reflecting constitutive transcript production. Our method agrees with the current standard approach, and in the restrictive regime where the standard method operates, also identifies rate constants not previously obtainable. Even without making any assumptions we obtain estimates of individual biochemical rate constants, or meaningful ratios of rate constants, in 91% of tested cases. In some cases our method identified all of the underlying rate constants. The framework developed here will be a powerful tool for deducing the contributions of particular molecular mechanisms to specific patterns of gene expression.

Dataset Information

PyBEL: a computational framework for Biological Expression Language.

Publications

PyBEL: a computational framework for Biological Expression Language.

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