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bioRxiv · 10.1101/2020.07.24.219196

Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs

Mishra, S.·Kumar, V.
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Abstract

Using gene-regulatory-networks based approach for single-cell expression profiles can reveal un-precedented details about the effects of external and internal factors. However, noise and batch effect in sparse single-cell expression profiles can hamper correct estimation of dependencies among genes and regulatory changes. Here we devise a conceptually different method using graph-wavelet filters for improving gene-network (GWNet) based analysis of the transcriptome. Our approach improved the performance of several gene-network inference methods. Most Importantly, GWNet improved consistency in the prediction of generegulatory-network using single-cell transcriptome even in presence of batch effect. Consistency of predicted gene-network enabled reliable estimates of changes in the influence of genes not highlighted by differential-expression analysis. Applying GWNet on the single-cell transcriptome profile of lung cells, revealed biologically-relevant changes in the influence of pathways and master-regulators due to ageing. Surprisingly, the regulatory influence of ageing on pneumocytes type II cells showed noticeable similarity with patterns due to effect of novel coronavirus infection in Human Lung.

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Mishra, S., Kumar, V.. 2020-07-25. Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs. https://doi.org/10.1101/2020.07.24.219196

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