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Nanopore Basecalling for Directed Evolution

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Derives a systematic approximation that turns an infinitesimal indel generator into a time-dependent pair HMM with nine transition probabilities reduced to four coupled differential equations, solved numerically (Runge‑Kutta). Uses moment‑matching / coarse‑graining by multiplying finite‑time transducers and collapsing states, improving relative‑entropy fit versus prior heuristics (including De Maio and TKF91 limits). Produces gap‑probability formulas that plug into automatic differentiation and can be fit to alignment data to estimate context‑dependent indel rates for proteins and genomes.

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  1. 0:00Start
  2. 0:25Why model indels phylogenetically?
  3. 6:47Thorne, Kishino & Felsenstein (1991)
  4. 9:51Continuous-time Markov processes Moment evolution approach
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