Ribosome Profiling: A Functional Genomics Approach to Study Translation in Hematologic Disease

Ribosome profiling (Ribo-seq) has transformed the study of translation by enabling transcriptome-wide, nucleotide-resolution measurement of ribosome occupancy. Since its introduction in 2009, Ribo-seq has expanded our understanding of the dynamic nature of translational regulation, revealing regulatory programs that cannot be inferred from transcript abundance alone. In hematologic systems, Ribo-seq has provided important insights into stress adaptation, malignant transformation, therapeutic resistance and translational programs that shape cellular phenotypes. In this review, we discuss the principles of ribosome profiling and highlight the biological contexts in which a Ribo-seq approach is particularly informative. We examine how Ribo-seq has advanced our understanding of selective translational programs, ribosome dysfunction, ribosome dynamics, and noncanonical translation. We also discuss emerging ribosome profiling strategies and complementary approaches that extend the interpretive power of translational profiling. Together, these advances establish ribosome profiling not simply as a method for measuring translation, but as a powerful functional genomics framework for understanding hematopoietic biology and identifying new therapeutic opportunities in hematologic disease.