Expected junction counts based mostly on the constant fee mannequin vs. the experimentally observed counts. Expected acceptor counts based on the fixed price mannequin vs. the experimentally observed counts. Expected donor counts based on the constant rate mannequin vs. the experimentally observed counts. Comparison of expected counts of the fixed fee model with observed experimental counts. Comparisons of the expected anticipated counts of the constant rate model with our noticed experimental counts are shown in Appendix 1—figures 16 , Appendix 1—figures 17 and Appendix 1—figures 18 .

Acceptor synthesis price vs. junction synthesis price throughout the same intron. Estimated half splicing time for donor and acceptor in addition to half-life for junctions based on simulated counts on the x-axis vs. the bottom truth.

No, a primary order kinetic model does not assume that every molecule is created initially of the time collection but that they're continuously synthesized and degraded in the course of the time series. Related to this point, our mannequin didn't think about time till 4sU will get obtainable to the transcription equipment . Note that this time has to be very short since labeled RNA was detected after 2 min labeling. Thank you for submitting your article 'Global donor and acceptor splicing site kinetics in human cells' for consideration by eLife. Your article has been reviewed by three peer reviewers, and the analysis has been overseen by Douglas Black as Reviewing Editor and James Manley as the Senior Editor.

Your article has been reviewed by three peer reviewers, and the evaluation has been overseen by a Reviewing Editor and a Senior Editor. In the interests of transparency, eLife includes the editorial choice letter and accompanying creator responses. A lightly edited version of the letter sent to the authors after peer evaluate is shown, indicating probably the most substantive issues; minor comments aren't usually included. Acceptor vs. donor delay estimation based on the mounted delay mannequin. Acceptor vs. donor synthesis rate estimation primarily based on the mounted delay mannequin.

A key assumption for the model fitting is that a hundred% of the label is incorporated. The authors ought to explicitly discover how lower ranges of labelling (e.g. 90, 50, 10%) have an effect on their results and conclusions. four) I discovered the splicing yield a part of the paper to be the most interpretable of the outcomes introduced. Again, nonetheless, none of this was validated with any extra quantitative measure such as digital droplet PCR. Thank you for submitting your work entitled 'Global two-step RNA splicing kinetics in human cells' for consideration by eLife.