Kenneth Hoehn

GitHub - hoehnlab/tyche Contribute to hoehnlab/tyche development by creating an account on GitHub.

These are a small fractions of the potential applications for TyCHE and SimBLE. To use them, you can get TyCHE here: github.com/hoehnlab/tyche. SimBLE: github.com/hoehnlab/sim.... There's also a vignette for using TyCHE from within our R package Dowser: dowser.readthedocs.io/en/latest/vi... (7/7)

Lastly, we used TyCHE to reconstruct the evolution of a hypermutating glioma tumor lineage and bacterial lung infection. In both cases, existing strict and relaxed clocks gave unrealistic trees but TyCHE's matched well with patient history. (6/7)

We then used TyCHE to analyze longitudinal BCRs from influenza vaccinees. TyCHE correctly inferred cycles of B cell evolution from primary GC to memory B cells to recall GCs, while existing models did not. It even inferred unsampled GC reactions at the start of each lineage! (5/7)

When applied to BCRs from HIV-infected donors, TyCHE correctly inferred the direction and patterns of germinal center to memory B cell formation. Existing models did not. Strikingly, TyCHE's time trees matched closely with clinically-estimated dates of infection. (4/7)

To validate TyCHE, we developed SimBLE, which simulates DNA sequences evolving under type-linked evolution, particularly B cells in germinal center reactions. We show that SimBLE simulates accurate BCRs, and that TyCHE outperforms existing clock models in BEAST (3/7)

TyCHE estimates trees, node dates, and cell types while allowing each subpopoulation (e.g. germinal center vs memory B cells) to evolve at a different rate. Because it's a BEAST2 package, TyCHE estimates all parameters using Bayesian MCMC. (2/7)

TyCHE enables time-resolved lineage tracing of heterogeneously-evolving populations Phylogenetic methods for cell lineage tracing have driven significant insights into organismal development, immune responses, and tumor evolution. While most methods estimate mutation trees, time-reso...

Excited to share my lab’s first preprint! We introduce TyCHE, which builds time-resolved lineage trees using sequences from populations evolving at drastically different rates. Examples include B cells, tumors, and some bacteria and viruses. (1/7) www.biorxiv.org/content/10.1...