Statistical Models for the Analysis of Isobaric Tags Multiplexed Quantitative Proteomics

D’Angelo, Gina; Chaerkady, Raghothama; Yao, Wen; Hızal, Deniz Baycın; Hess, Sonja; Zhao, Wei; Lekstrom, Kristen; Guo, Xiang; White, Wendy I.; Roskos, Lorin; Bowen, Michael A.; Yang, Haiou

doi:10.1021/acs.jproteome.6b01050

Cited by 34 publications

(31 citation statements)

References 45 publications

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“…Day 1 was not included as we did not detect any DHQ in those samples and tandem mass tags for labeling was, at the time, limited to 10 tags. We used the eBayes() function in the R limma package (Ritchie et al, 2015) (version 3.36.5) to determine significant differences between groups in each tissue (D'Angelo et al, 2017). Tissues were analysed separately as they were TMT-labeled and run separately on the mass spectrometer.…”

Section: Discussionmentioning

confidence: 99%

Rapid toxin sequestration modifies poison frog physiology

O’Connell

Paulo

et al. 2020

Preprint

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Poison frogs sequester their chemical defenses from their diet of leaf litter arthropods for defense against predation. Little is known about poison frog physiological adaptations that confer this unusual ability to bioaccumulate dietary alkaloids from the intestines to skin glands for storage. We conducted an alkaloid-feeding experiment with the Diablito poison frog (Oophaga sylvatica) to determine how quickly toxins are accumulated and how toxins impact frog physiology using quantitative proteomics. Diablito frogs were able to rapidly accumulate the alkaloid decahydroquinoline to the skin storage glands within four days of dietary exposure, with decahydroquinoline also detected in the intestines and liver. Alkaloid exposure impacted tissue physiology, with protein abundance shifting in the intestines, liver, and skin. Many proteins that increased in abundance with toxin accumulation are plasma glycoproteins, including components of the complement system and the toxin-binding protein saxiphilin. Other protein classes that change in abundance with toxin accumulation are membrane proteins involved in small molecule transport and metabolism, including ABC transporters, solute carrier proteins, and cytochrome P450s. Overall, this work shows that poison frogs can rapidly accumulate alkaloid toxins, which alter carrier protein abundance, initiate an immune response, and alter small molecule transport and metabolism dynamics across tissues. More broadly, this study suggests that acute changes in diet may quickly change the chemical arsenal and physiology of poison frogs, which may have important consequences in their defense against predation.

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Section: Discussionmentioning

confidence: 99%

Rapid toxin sequestration modifies poison frog physiology

O’Connell

Paulo

et al. 2020

Preprint

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“…For the TMT quantification, the LIBRA (Trans-proteome pipeline, version 4.2.1) program was used to quantitate the label-based quantitation peptide and protein identifications. A fold change greater than 1.2 or less than 0.8 was considered statistically significant 51 , 52 .…”

Section: Methodsmentioning

confidence: 99%

The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory

Lee

Bang

Yang

et al. 2018

Sci Rep

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Established fear memory becomes vulnerable to disruption after memory retrieval and extinction; this labile state is critical for inhibiting the return of fear memory. However, the labile state has a very narrow time window after retrieval, and underlying molecular mechanisms are not well known. To that end, we isolated the hippocampus immediately after fear memory retrieval and performed proteomics. We identified Neurobeachin (NBEA), an autism-related regulator of synaptic protein trafficking, to be upregulated after contextual fear memory retrieval. NBEA protein expression was rapid and transient after fear memory retrieval at the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of NBEA expression was blocked by inhibition of the mammalian target of rapamycin (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea shRNA knockdown showed normal fear acquisition and contextual fear memory but impaired extinction, suggesting an important role of Nbea in fear memory extinction processes. Consistently, Nbea heterozygotes showed normal fear acquisition and fear memory recall but showed impairment in extinction. Our data suggest that NBEA is necessary either for induction of memory lability or for the physiological process of memory extinction.

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“…Benchmark dataset D'Angelo et al performed a comparison of different approaches to analyse TMT datasets 19 .…”

Section: Performance Tests By Reprocessing Public Datamentioning

confidence: 99%

IsoProt: A complete and reproducible workflow to analyse iTRAQ/TMT experiments

Griss

Vinterhalter

Schwämmle

2018

Preprint

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Reproducibility has become a major concern in biomedical research. In proteomics, bioinformatic workflows can quickly consist of multiple software tools each with its own set of parameters. Their usage involves the definition of often hundreds of parameters as well as data operations to ensure tool interoperability. Hence a manuscript’s methods section is often insufficient to completely describe and reproduce a data analysis workflow. Here we present IsoProt: A complete and reproducible bioinformatic workflow deployed on a portable container environment to analyse data from isobarically-labeled, quantitative proteomics experiments. The workflow uses only open source tools and provides a user-friendly and interactive browser interface to configure and execute the different operations. Once the workflow is executed, the results including the R code to perform statistical analyses can be downloaded as an HTML or PDF document providing a complete record of the performed analyses. IsoProt therefore represents a reproducible bioinformatics workflow that will yield identical results on any computer platform.

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Statistical Models for the Analysis of Isobaric Tags Multiplexed Quantitative Proteomics

Cited by 34 publications

References 45 publications

Rapid toxin sequestration modifies poison frog physiology

Rapid toxin sequestration modifies poison frog physiology

The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory

IsoProt: A complete and reproducible workflow to analyse iTRAQ/TMT experiments

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