Zhisong He | Search bioRxiv

bioRxiv2016

Cell type composition is the primary - but far from the only - power shaping temporal transcriptome of human brains

The functions of human brains highly depend on the precise temporal regulation of gene expression, and substantial transcriptome changes across lifespan have been observed. While cell type composition is known to be temporally variable in brains, it remains unclear whether it is the primary cause of age-related transcriptome changes. Here, taking advantage of published human brain single-cell RNA-seq data, we applied a two-step transcriptome deconvolution procedure to the public age series RNA-seq data to quantify the contribution of cell type composition in shaping the temporal transcriptome in human brains. We estimated that composition change contributed to around 25% of the total variance and was the primary factor of age-related transcriptome changes. On the other hand, genes with substantial composition-independent temporal expression changes were also observed, which had diverged expression properties, functions and regulators as genes with temporal expression changes related to composition. This indicates a second independent mechanism shaping the human brains temporal transcriptome properties, which is important for human brain functions.

Bioinformatics↗

bioRxiv2014

Evaluating intra- and inter-individual variation in the human placental transcriptome

BackgroundGene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta.\n\nResultsWe estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%).\n\nConclusionWe apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.

Genomics↗