one unanticipated downside of grad school was that it took the fun out of reading for me. this year, i started picking up books again and fell back in love 🥹 #booksky

we found pronounced cell state-dependent genetic variation in pathways related to interferon responses and oxidative phosphorylation, two pathways we also observed to be significantly associated with COVID-19 disease severity 6/n

we then hypothesized that these patient-specific effects may be driven by heterogeneity in functional cell states dynamically regulated in cis. to test this, we mapped interaction eQTL at the single-cell level using poisson mixed effects models and a continuous measure of cell state 5/n

to confirm whether these genetic effects were conditional on the active infection state, we mapped eQTL in recovered COVID-19 patients. indeed, patient-specific genetic effects dissipated as infection resolved, suggesting that distinct and dynamic gene regulatory networks are at play 4/n

via standard eQTL mapping, we show that disease state-specific genetic effects are abundant (on average, 15% of eGenes across cell types), with the vast majority of these (~90%) representing eQTL observed only in acute COVID-19 patients rather than in healthy individuals 3/n

using single-cell RNA-seq, we profiled PBMCs from acute patients sampled prior to the rollout of vaccines and during various longitudinal follow-up time points. with this data, we investigated cell type-specific, disease state-specific, and cell state-dependent gene regulatory heterogeneity 2/n