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Text: What is even more surprising is the observed low reaction efficiency in the study by Safra et al. (2017), which significantly decreases the sensitivity of m 1 A detection. For the two known m 1 A sites in 16S and 28S rRNAs, a ∼65% and ∼63% mismatch rate still remains after the Dimroth reaction in the **data** of Safra et al. (2017), respectively, compared to a remaining mutation of ∼1% after AlkB treatment (Fig. 2D) for both sites. Similarly, for m 1 A575 in 12S mt-rRNA, which is identified de novo and biochemically validated by Li and coworkers (see Figs. 4C and S5B in Li et al. 2017) but missed by Safra et al. (2017), both their signal (IP sample) and the validation (IP + demthylation sample) **data** are of limited quality (Fig. 2E,F). Considering that m 1 A sites in abundant rRNA were even missed, it is anticipated that detection of m 1 A sites in low abundance mRNA would be very difficult in the Safra et al. (2017) study. More differences in experimental procedures that lead to the different qualities of the sequencing **data** sets by the two studies have been described in this technology preview (Dominissini and Rechavi 2017). Schwartz (2018) also mentioned that they found "no significant change in stop rates" in their SSIII **data** and hence FIGURE 2. Reanalyses of sequencing **data** by Safra et al. (2017) provide an explanation as to why they failed to identify the majority of m 1 A in mRNA. (A) Reads' coverage for the eight TRMT6/61A sites (detected in both studies) in different sequencing **data** sets. The inset box in each panel provides a zoomed-in view of reads' coverage by Safra and coworkers. (B) Reads' coverage for the 44 TRMT6/61A sites and 196 "reclassified" TSS sites in different sequencing **data** sets. All these sites are missed in the study by Safra and coworkers. The inset box in each panel provides a zoomedin view of reads' coverage by Safra et al. (2017). (C) Reads' duplication levels and rRNA contamination levels of different sequencing **data** sets.<|eot_id|><|start_header_id|>assistant<|end_header_id|>

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