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Molecular mechanisms of system responses to novel stimuli are predictable from public data.

ABSTRACT: Systems scale models provide the foundation for an effective iterative cycle between hypothesis generation, experiment and model refinement. Such models also enable predictions facilitating the understanding of biological complexity and the control of biological systems. Here, we demonstrate the reconstruction of a globally predictive gene regulatory model from public data: a model that can drive rational experiment design and reveal new regulatory mechanisms underlying responses to novel environments. Specifically, using ? 1500 publically available genome-wide transcriptome data sets from Saccharomyces cerevisiae, we have reconstructed an environment and gene regulatory influence network that accurately predicts regulatory mechanisms and gene expression changes on exposure of cells to completely novel environments. Focusing on transcriptional networks that induce peroxisomes biogenesis, the model-guided experiments allow us to expand a core regulatory network to include novel transcriptional influences and linkage across signaling and transcription. Thus, the approach and model provides a multi-scalar picture of gene dynamics and are powerful resources for exploiting extant data to rationally guide experimentation. The techniques outlined here are generally applicable to any biological system, which is especially important when experimental systems are challenging and samples are difficult and expensive to obtain-a common problem in laboratory animal and human studies.

SUBMITTER: Danziger SA

PROVIDER: S-EPMC3919619 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Molecular mechanisms of system responses to novel stimuli are predictable from public data.

Danziger Samuel A SA Ratushny Alexander V AV Smith Jennifer J JJ Saleem Ramsey A RA Wan Yakun Y Arens Christina E CE Armstrong Abraham M AM Sitko Katherine K Chen Wei-Ming WM Chiang Jung-Hsien JH Reiss David J DJ Baliga Nitin S NS Aitchison John D JD

Nucleic acids research 20131031 3

Systems scale models provide the foundation for an effective iterative cycle between hypothesis generation, experiment and model refinement. Such models also enable predictions facilitating the understanding of biological complexity and the control of biological systems. Here, we demonstrate the reconstruction of a globally predictive gene regulatory model from public data: a model that can drive rational experiment design and reveal new regulatory mechanisms underlying responses to novel enviro ...[more]

PMID: 24185701

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Project description:Contextual information triggers predictions about the content ("what") of environmental stimuli to update an internal generative model of the surrounding world. However, visual information dynamically changes across time, and temporal predictability ("when") may influence the impact of internal predictions on visual processing. In this magnetoencephalography (MEG) study, we investigated how processing feature specific information ("what") is affected by temporal predictability ("when"). Participants (N = 16) were presented with four consecutive Gabor patches (entrainers) with constant spatial frequency but with variable orientation and temporal onset. A fifth target Gabor was presented after a longer delay and with higher or lower spatial frequency that participants had to judge. We compared the neural responses to entrainers where the Gabor orientation could, or could not be temporally predicted along the entrainer sequence, and with inter-entrainer timing that was constant (predictable), or variable (unpredictable). We observed suppression of evoked neural responses in the visual cortex for predictable stimuli. Interestingly, we found that temporal uncertainty increased expectation suppression. This suggests that in temporally uncertain scenarios the neurocognitive system invests less resources in integrating bottom-up information. Multivariate pattern analysis showed that predictable visual features could be decoded from neural responses. Temporal uncertainty did not affect decoding accuracy for early visual responses, with the feature specificity of early visual neural activity preserved across conditions. However, decoding accuracy was less sustained over time for temporally jittered than for isochronous predictable visual stimuli. These findings converge to suggest that the cognitive system processes visual features of temporally predictable stimuli in higher detail, while processing temporally uncertain stimuli may rely more heavily on abstract internal expectations.

Dataset Information

Molecular mechanisms of system responses to novel stimuli are predictable from public data.

Publications

Molecular mechanisms of system responses to novel stimuli are predictable from public data.

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