Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia

Post-transcriptional regulations play crucial roles in gene expression, but their global impact in acute myeloid leukemia (AML) remains poorly understood. Here, we perform an integrative analysis of transcriptomic and proteomic data from 44 AML samples to uncover the determinants of protein-to-mRNA-ratios (PTRs), a metric summarizing post-transcriptional regulatory processes. Using over a thousand proxies related to mRNA sequestration, translation efficiency, and RNA/protein stability, multivariate regression reveals key features driving PTRs. Our findings show that PTRs are conserved between AML samples and human tissues, underscoring the universality of underlying mechanisms. Furthermore, we show that the shadow proteome, consisting of genes frequently undetectable by mass spectrometry, can be partially attributed to low predicted PTRs.Due to the lack of existing tools, these post-transcriptional mechanisms remained in the blind spot of proteogenomic analysis. To bridge this gap, we developed POSTCODE, a tool for annotating omics datasets with PTR-related proxies, enabling the detection of post-transcriptional regulation changes. Applying this tool to AML datasets enables a better understanding of the mechanisms underlying differential expression, including alterations in proteostasis, translation, RNA stability or transcript localization. Our study provides a comprehensive resource for monitoring post-transcriptional regulation, paving the way for the identification of new precision medicine strategies.