13,839 research outputs found
BioSimulator.jl: Stochastic simulation in Julia
Biological systems with intertwined feedback loops pose a challenge to
mathematical modeling efforts. Moreover, rare events, such as mutation and
extinction, complicate system dynamics. Stochastic simulation algorithms are
useful in generating time-evolution trajectories for these systems because they
can adequately capture the influence of random fluctuations and quantify rare
events. We present a simple and flexible package, BioSimulator.jl, for
implementing the Gillespie algorithm, -leaping, and related stochastic
simulation algorithms. The objective of this work is to provide scientists
across domains with fast, user-friendly simulation tools. We used the
high-performance programming language Julia because of its emphasis on
scientific computing. Our software package implements a suite of stochastic
simulation algorithms based on Markov chain theory. We provide the ability to
(a) diagram Petri Nets describing interactions, (b) plot average trajectories
and attached standard deviations of each participating species over time, and
(c) generate frequency distributions of each species at a specified time.
BioSimulator.jl's interface allows users to build models programmatically
within Julia. A model is then passed to the simulate routine to generate
simulation data. The built-in tools allow one to visualize results and compute
summary statistics. Our examples highlight the broad applicability of our
software to systems of varying complexity from ecology, systems biology,
chemistry, and genetics. The user-friendly nature of BioSimulator.jl encourages
the use of stochastic simulation, minimizes tedious programming efforts, and
reduces errors during model specification.Comment: 27 pages, 5 figures, 3 table
A local regulatory network around three NAC transcription factors in stress responses and senescence in Arabidopsis leaves
A model is presented describing the gene regulatory network surrounding three similar NAC transcription factors that have roles in Arabidopsis leaf senescence and stress responses. ANAC019, ANAC055 and ANAC072 belong to the same clade of NAC domain genes and have overlapping expression patterns. A combination of promoter DNA/protein interactions identified using yeast 1-hybrid analysis and modelling using gene expression time course data has been applied to predict the regulatory network upstream of these genes. Similarities and divergence in regulation during a variety of stress responses are predicted by different combinations of upstream transcription factors binding and also by the modelling. Mutant analysis with potential upstream genes was used to test and confirm some of the predicted interactions. Gene expression analysis in mutants of ANAC019 and ANAC055 at different times during leaf senescence has revealed a distinctly different role for each of these genes. Yeast 1-hybrid analysis is shown to be a valuable tool that can distinguish clades of binding proteins and be used to test and quantify protein binding to predicted promoter motifs
Detection of regulator genes and eQTLs in gene networks
Genetic differences between individuals associated to quantitative phenotypic
traits, including disease states, are usually found in non-coding genomic
regions. These genetic variants are often also associated to differences in
expression levels of nearby genes (they are "expression quantitative trait
loci" or eQTLs for short) and presumably play a gene regulatory role, affecting
the status of molecular networks of interacting genes, proteins and
metabolites. Computational systems biology approaches to reconstruct causal
gene networks from large-scale omics data have therefore become essential to
understand the structure of networks controlled by eQTLs together with other
regulatory genes, and to generate detailed hypotheses about the molecular
mechanisms that lead from genotype to phenotype. Here we review the main
analytical methods and softwares to identify eQTLs and their associated genes,
to reconstruct co-expression networks and modules, to reconstruct causal
Bayesian gene and module networks, and to validate predicted networks in
silico.Comment: minor revision with typos corrected; review article; 24 pages, 2
figure
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
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