Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Time series RNA-seq of Naïve CD4 positive T-cells undergoing differentiation towards T-helper 1.

ABSTRACT: In eukaryotes, mRNA abundance is often a poor proxy for protein abundance. Despite this, the majority of methods used to dissect function in mammalian biology involve measurements of mRNA, with the assumption that changes observed at the mRNA level are reflected at the protein level. The inability to predict protein abundance from mRNA abundance is a major limitation when dissecting the relationship between genotype and phenotype in mammals. To understand the effect of cell-type, splice-variant selection and translation rate on the relationship between mRNA and protein abundance, we performed RNA-sequencing and mass-spectrometry proteomics of primary human naïve CD4+ T helper (NTH) cells at six time points during differentiation into T-helper type 1 (TH1) cells. For the RNA- sequencing, NTH cells were isolated from Human blood donors, subjected to T-helper 1 stimulation (anti-CD3/CD28, IL2 and IL12) for 0.5, 1, 2, 6 and 24 hours. At each time point cells were harvested, snap frozen and stored at -80 degrees Celsius. RNA was isolated from each sample and sequenced on an illumina 2500 instrument. By combining the information from the RNA- sequencing and the proteomics we constructed a simple mRNA-protein model, in which protein expression was defined as a linear combination of the splice variants of a gene, with a time-delay accounting for the dynamical effect induced by post-transcriptional processes and protein synthesis. This simple dynamical model resulted in a gene-protein correlation of rhoTH1 = 0.86, significantly higher than previously reported gene-protein prediction models in mammals.

ORGANISM(S): Homo sapiens

SUBMITTER: Olof Rundquist

PROVIDER: E-MTAB-7775 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Using high-throughput multi-omics data to investigate structural balance in elementary gene regulatory network motifs.

Zenere Alberto A Rundquist Olof O Gustafsson Mika M Altafini Claudio C

Bioinformatics (Oxford, England) 20211201 1

<h4>Motivation</h4>The simultaneous availability of ATAC-seq and RNA-seq experiments allows to obtain a more in-depth knowledge on the regulatory mechanisms occurring in gene regulatory networks. In this article, we highlight and analyze two novel aspects that leverage on the possibility of pairing RNA-seq and ATAC-seq data. Namely we investigate the causality of the relationships between transcription factors, chromatin and target genes and the internal consistency between the two omics, here m ...[more]

PMID: 34383882

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Project description:Quantitative studies of the P. falciparum transcriptome have shown that the tightly controlled progression of the parasite through the intraerythrocytic developmental cycle (IDC) is accompanied by a continuous gene expression cascade where most expressed genes exhibit a single transcriptional peak. Since proteins represent the decisive business end of gene expression, understanding the correlation between mRNA and protein levels is crucial for inferring biological activity from transcriptional gene expression data. While pertinent studies on other organisms show that as little as 20-40% of protein abundance variation may be attributable to corresponding mRNA levels, the situation in Plasmodium is further complicated by the dynamic nature of the cyclic gene expression cascade where the mRNA levels of most genes change constantly during the IDC. In this study, we simultaneously determined mRNA and protein abundance profiles for P. falciparum parasites during the IDC at 2-hour resolution based on spotted oligonucleotide microarrays and 2D-protein gels in combination with DIGE fluorescent dyes. Intriguingly, most proteins are represented by more than one isoform, presumably due to post-translational modifications. Analysis of 366 protein abundance profiles and the corresponding mRNA levels shows that in 67.2% of cases the protein abundance peaks at least 8 hours after the mRNA level peak. While it may be tempting to interpret this as evidence for widespread post-transcriptional gene regulation additional analyses including computer modeling demonstrate that in >60% of these cases the observed protein profiles including the peak lag times could arise as a consequence of the corresponding mRNA levels when simple translation and degradation dynamics are assumed. We further characterize and illustrate these dynamics and show that even human host proteins within the parasite may be subject to similar dynamics as their parasite counterparts. 24 timepoint samples were harvested from a tightly synchronous 6.5 liter biofermenter culture of P. falciparum (Dd2) at 2-hour intervals during one entire intraerythrocytic developmental cycle and compared against a 3D7 RNA reference pool.

Dataset Information

Time series RNA-seq of Naïve CD4 positive T-cells undergoing differentiation towards T-helper 1.

Publications

Using high-throughput multi-omics data to investigate structural balance in elementary gene regulatory network motifs.

Similar Datasets

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