The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct RNA sequencing, N6-methyladenosine (m6A) RNA modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Specifically, we find that our algorithm, trained with m6A-modified and unmodified synthetic sequences, can predict m6A RNA modifications with ~90% accuracy. We then extend our findings to yeast data sets, finding that our method can identify m6A RNA modifications in vivo with an accuracy of 87%. Moreover, we further validate our method by showing that these ‘errors’ are typically not observed in yeast ime4-knockout strains, which lack m6A modifications. Our results open avenues to investigate the biological roles of RNA modifications in their native RNA context.
Two issues long debated among Pacific and American prehistorians are (
i
) whether there was a pre-Columbian introduction of chicken (
Gallus gallus
) to the Americas and (
ii
) whether Polynesian contact with South America might be identified archaeologically, through the recovery of remains of unquestionable Polynesian origin. We present a radiocarbon date and an ancient DNA sequence from a single chicken bone recovered from the archaeological site of El Arenal-1, on the Arauco Peninsula, Chile. These results not only provide firm evidence for the pre-Columbian introduction of chickens to the Americas, but strongly suggest that it was a Polynesian introduction.
Nanopore RNA sequencing shows promise as a method for discriminating and identifying different RNA modifications in native RNA. Expanding on the ability of nanopore sequencing to detect N6-methyladenosine (m6A), we show that other modifications, in particular pseudouridine (Ѱ) and 2'-O-methylation (Nm), also result in characteristic base-calling 'error' signatures in the nanopore data. Focusing on Ѱ modification sites, we detect known and uncover previously unreported Ѱ sites in mRNAs, ncRNAs and rRNAs, including a Pus4dependent Ѱ modification in yeast mitochondrial rRNA. To explore the dynamics of pseudouridylation, we treat yeast cells with oxidative, cold and heat stresses and detect heatsensitive Ѱ-modified sites in snRNAs, snoRNAs and mRNAs. Finally, we develop a software, nanoRMS, that estimates per-site modification stoichiometries by identifying single-molecule reads with altered current intensity and trace profiles. This work demonstrates that Nm and Ѱ RNA modifications can be detected in cellular RNAs and that Ѱ RNA can be identified in a quantitative manner by nanopore sequencing of native RNA.
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This paper presents an optimal control design for currentfed induction motor drives. The problem to be considered is to find a feedback control that minimizes a generalized convex energy cost function including the stored magnetic energy and the coil losses, while satisfying torque tracking control objectives. Necessary and sufficient conditions for optimality are established. It is shown here that all the stationary solutions can be obtained analytically and are uniquely defined. It is also shown that closed-forms for dynamic suboptimal solutions can also be obtained. The optimal solutions turn out to imply nonstandard timevarying (reference depending) norm flux operations in opposition to well established field-oriented control that operates with constant flux norm.
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