Seidel et al., Nature Communications - SciPhy is a BEAST2-integrated Bayesian framework that models sequential CRISPR‑based insertion edits to jointly infer time-scaled single-cell lineage trees, editing dynamics, and population growth. The authors validate SciPhy on simulations and apply it to HEK293T monoclonal expansion and murine gastruloid datasets, showing improved tree and branch-length inference relative to UPGMA and enabling phylodynamic estimates of growth. Key terms: Bayesian phylogenetics, lineage tracing, CRISPR, DNA Typewriter, phylodynamics.

Study Highlights:
SciPhy implements a mechanistic model of ordered, irreversible insertions with per-tape clock rates and insertion probabilities and computes the likelihood using a pruning algorithm within BEAST2. Validation on calibrated simulations shows correct posterior coverage and high correlations between true and inferred editing and tree parameters. Application to HEK293T and gastruloid data recovers per-tape edit rates and preferential insert probabilities, infers growth rates including time-varying dynamics in gastruloid development, and yields more accurate topologies and branch lengths than UPGMA. The framework reports uncertainty and enables joint phylodynamic analysis of lineage tracing data.

Conclusion:
A mechanistic, order-aware Bayesian model for sequential genome-editing lineage recorders improves reconstruction of time-calibrated cell lineage trees, quantifies editing biases and clock rates, and enables inference of cell population dynamics from single-cell lineage tracing data.

Music:
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Article title:
SciPhy: A Bayesian phylogenetic framework using sequential genetic lineage tracing data

First author:
Seidel

Journal:
Nature Communications

DOI:
10.1038/s41467-026-73377-6

Reference:
Seidel, S., Zwaans, A., Regalado, S. et al. SciPhy: A Bayesian phylogenetic framework using sequential genetic lineage tracing data. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73377-6

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-06-20.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantive auditing of the transcript's description of SciPhy's mechanistic model (ordered CRISPR edits), BEAST2 implementation, validation results, HEK293T monoclonal expansion, gastruloid development with CHIR treatment, and discussed limitations and computational considerations.
- transcript topics: Mechanistic editing model with ordered inserts; BEAST2 integration and likelihood calculation; Editing rate clock rates and insertion probabilities; Validation: in-silico, HEK293T monoclonal expansion; Insertion bias: CAT vs GCG; Growth dynamics and phylodynamic inference

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- SciPhy is a Bayesian framework implemented in BEAST 2 for jointly estimating time-scaled phylogenies and cell population parameters using sequential, ordered CRISPR edits (DNA Tape
- The model uses per-tape clock rates and insertion probabilities to describe editing dynamics.
- Felsenstein pruning is used for likelihood calculation across the phylogeny with tape data.
- HEK293T monoclonal expansion dataset (~25 days) used to validate editing dynamics and growth rates; observed CAT insertions around 16% and GCG around ≤1%.
- Clock rates around 0.15 d^-1 on most tapes, equating to roughly 4 edits per tape over the experiment duration.
- SciPhy produced more accurate time-calibrated trees and differentiated branch lengths compared to UPGMA on both simulated and real data.

QC result: Pass.