Tradeoffs between Dense and Replicate Sampling Strategies for High-Throughput Time Series Experiments

Sefer, Emre; Kleyman, Michael; Bar‐Joseph, Ziv

doi:10.1016/j.cels.2016.06.007

Cited by 29 publications

(25 citation statements)

References 26 publications

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“…Most of these, however, use either static or traditional time series analyses on self-contained temporal data sets with a limited number of time points (Zinman et al, 2013). Generating additional time points for such analyses involves a cost-benefit tradeoff that has recently been explored (Sefer et al, 2016). Although there is typically greater benefit from adding time points at the expense of replicates, the costs of sampling adequately to identify medically-relevant changes in temporal dynamics may be prohibitive, especially when the dynamic 13 processes are not already well understood.…”

Section: Resultsmentioning

confidence: 99%

TEMPO: Detecting Pathway-Specific Temporal Dysregulation of Gene Expression in Disease

Pietras

Ocitti

Slonim

2019

Preprint

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While many transcriptional profiling experiments measure dynamic processes that change over time, few include enough time points to adequately capture temporal changes in expression. This is especially true for data from human subjects, for which relevant samples may be hard to obtain, and for developmental processes where dynamics are critically important. Although most expression data sets sample at a single time point, it is possible to use accompanying temporal information to create a virtual time series by combining data from different individuals.We introduce TEMPO, a pathway-based outlier detection approach for finding pathways showing significant temporal changes in expression patterns from such combined data. We present findings from applications to existing microarray and RNA-seq data sets. TEMPO identifies temporal dysregulation of biologically relevant pathways in patients with autism spectrum disorders, Huntington's disease, Alzheimer's disease, and COPD. Its findings are distinct from those of standard temporal or gene set analysis methodologies.Overall, our experiments demonstrate that there is enough signal to overcome the noise inherent in such virtual time series, and that a temporal pathway approach can identify new functional, temporal, or developmental processes associated with specific phenotypes.Availability: An R package implementing this method and full results tables are available at bcb.cs.tufts.edu/tempo/.

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Section: Resultsmentioning

confidence: 99%

TEMPO: Detecting Pathway-Specific Temporal Dysregulation of Gene Expression in Disease

Pietras

Ocitti

Slonim

2019

Preprint

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“…The dose response, measured as the expression trend across doses, was the primary outcome. Such design provides greater statistical power in gene expression profiling than fewer dose levels with more replicates per dose level (34). For example, ten dose levels with one mouse each would provide 80% power to detect a correlation between dose and gene expression of r > 0.95 (Spearman) with an uncorrected p value of ~0.0002.…”

Section: Resultsmentioning

confidence: 99%

Distinct vascular genomic response of proton and gamma radiation

Emanuela

Sarantopoulou

et al. 2018

Preprint

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Purpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge. Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 -200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results. While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes; q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation; p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships. Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

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“…The frequency of collection will necessarily depend on the duration of the response and practical and financial considerations. Increasing density will necessarily increase the correlative power of the study without negatively affecting the observation of transiently expressed genes (Supplementary Figure S7B & (75)). However, replication ensures uniformity of the biology underlying the process in question (figure 1B), thus enabling confident dissection of transient or periodic gene expression patterns from noise.…”

Section: Discussionmentioning

confidence: 99%

High temporal resolution of gene expression dynamics in developing mouse embryonic stem cells

Signal

et al. 2016

Preprint

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Investigations of transcriptional responses during developmental transitions typically use time courses with intervals that are not commensurate with the timescales of known biological processes. Moreover, such experiments typically focus on protein-coding transcripts, ignoring the important impact of long noncoding RNAs. We evaluated coding and noncoding expression dynamics at high temporal resolution (6-hourly) in differentiating mouse embryonic stem cells and report the effects of increased temporal resolution on the characterization of the underlying molecular processes. We present a refined resolution of global transcriptional alterations, including regulatory network interactions, coding and noncoding gene expression changes as well as alternative splicing events, many of which cannot be resolved by existing coarse developmental time--courses. We describe novel short lived and cycling patterns of gene expression and temporally dissect ordered gene expression at bidirectional promoters and responses to transcription factors. These findings demonstrate the importance of temporal resolution for understanding gene interactions in mammalian systems.Links to dataData has been deposited into GEO: The Reviewer access link is: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=cnglummejbkltyj@acc=GSE75028

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Tradeoffs between Dense and Replicate Sampling Strategies for High-Throughput Time Series Experiments

Cited by 29 publications

References 26 publications

TEMPO: Detecting Pathway-Specific Temporal Dysregulation of Gene Expression in Disease

TEMPO: Detecting Pathway-Specific Temporal Dysregulation of Gene Expression in Disease

Distinct vascular genomic response of proton and gamma radiation

High temporal resolution of gene expression dynamics in developing mouse embryonic stem cells

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