MLC-Seq: de novo Sequencing of Full-Length tRNAs and Quantitative Mapping of Multiple RNA Modifications

Despite the extensive use of next-generation sequencing of RNA, simultaneous sequencing and quantitative mapping of multiple RNA modifications remain challenging. Herein, we develop MLC-Seq, a mass spectrometry-based direct sequencing method allowing for simultaneously unravelling the RNA sequences and quantitatively mapping different tRNA nucleotide modifications site-specifically. Importantly, MLC-Seq reveals the stoichiometric changes of tRNA modifications upon treatment with the dealkylating enzyme AlkB, and led to the discovery of new nucleotide modifications.

Voxel-Wise Quantitative Mapping of the Brain Association Ability

The association cortices of the brain are essential for integrating multimodal information that subserves complex and high-order cognitive functions. To delineate the changing pattern of associative cortices can provide critical insight into brain development, aging, plasticity, and disease-triggered functional abnormalities. However, how to quantitatively characterize the association capability of the brain is elusive. Here, we developed a new method of association index (Asso) at the voxel level to quantitatively characterize the brain association ability. Using the Asso method, we found high Asso values in association cortical networks, and low values in visual and limbic networks, suggesting a pattern of significant gradient distribution in neural functions. The spatial distribution patterns of Asso show high similarities across different thresholds suggesting that Asso mapping is a threshold-free method. In addition, compared with functional connectivity strength, i.e., degree centrality method, Asso mapping showed different patterns for association cortices and primary cortices. Finally, the Asso method was applied to investigate aging effects and identified similar findings with previous studies. All these results indicated that Asso can characterize the brain association patterns effectively and open a new avenue to reveal a neural basis for development, aging, and brain disorders.