dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025If you’re interested in trying MULTI-ATAC yourself, have a look at the protocol in the SI, and reach out to me for further details about oligos and barcode sequences. 000
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025MULTI-ATAC has already been successfully applied in other contexts as well. In this work, my collaborator Katya used MULTI-ATAC to probe the mechanisms by which deleterious mutations accumulate in the mitochondrial genome during aging: www.biorxiv.org/content/10.1...biorxiv.orgSelection promotes age-dependent degeneration of the mitochondrial genomeSomatic mutations in mitochondrial genomes (mtDNA) accumulate exponentially during aging. Using single cell sequencing, we characterize the spectrum of age-accumulated mtDNA mutations in mouse and hum... 100
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025By including multiple replicates and doses per drug, we discover high-confidence drug-responsive chromatin regions and genes. We show that EZH2 degradation via MS177 coincides with up-regulation of NF-kB signaling, and SWI/SNF perturbation elicits a potent type I interferon response. 100
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025MULTI-ATAC is also compatible with the 10x Genomics Multiome kit. To demonstrate the type of high-throughput experiment enabled by MULTI-ATAC, we perform a 96-plex multiomic drug assay comparing inhibition and degradation of different epigenetic remodelers in a model of primary immune activation. 100
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025To combat this, we re-designed our MULTI-seq method and optimized it to enable pooled transposition of barcoded nuclei on the 10x Genomics scATAC-seq platform. We show that pooled transposition with MULTI-ATAC completely negates the batch effects that arise from processing samples separately. 100
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025The effect of variable transposition is well-established in bulk ATAC data but surprisingly has not to our knowledge been examined in scATAC-seq. This is especially important to consider when unique samples (i.e., different patients, disease states, etc.) are transposed in a parallel format. 100
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025For example, we see that variability in Tn5:nuclei ratios unsurprisingly skews per-nucleus fragment yields. However, this impacts dimensionality reduction and - importantly - even biases cell type recovery. 110
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025scATAC-seq data across different technologies and sample types suffer from batch effects that are linked to transposition reaction conditions and directly impact biological interpretation. 100
dconrad1.bsky.social @dconrad1.bsky.social · 20/02/2025Happy to share that the preprint to our new scATAC-seq multiplexing method, MULTI-ATAC, is officially online: www.biorxiv.org/content/10.1...biorxiv.orgReducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATACLarge-scale scATAC-seq experiments are challenging because of their costs, lengthy protocols, and confounding batch effects. Several sample multiplexing technologies aim to address these challenges, b... 263
