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Deciphering Cell Fate and Clonal Dynamics via Integrative Single-Cell Lineage Modeling.

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Summary
This summary is machine-generated.

Clonotrace integrates gene expression and lineage barcodes to improve cell fate inference. This computational framework enhances understanding of cell differentiation dynamics, particularly for T cells in clinical settings.

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Area of Science:

  • Single-cell biology
  • Computational biology
  • Immunology

Background:

  • Single-cell technologies enable joint measurement of molecular states and clonal identities.
  • Current computational methods for cell differentiation often overlook lineage information from barcodes.
  • T cell analysis, crucial in clinical settings, can benefit from integrating transcriptional and clonal data.

Purpose of the Study:

  • To develop a computational framework, Clonotrace, that jointly models gene expression and clonotype information.
  • To improve the fidelity of inferring cell state transitions and fate biases.
  • To provide a broadly applicable tool for lineage-barcoded single-cell datasets.

Main Methods:

  • Developed Clonotrace, a computational framework integrating gene expression and clonotype data.
  • Applied Clonotrace to diverse systems including T cells, hematopoietic differentiation, and cancer models.
  • Validated the framework's ability to reveal differentiation hierarchies and identify fate-determining genes.

Main Results:

  • Clonotrace infers cell state transitions and fate biases with higher fidelity than methods relying solely on transcriptional similarity.
  • The framework successfully revealed differentiation hierarchies in various biological systems.
  • Identified candidate fate-determining genes driving lineage commitment across different cell types.

Conclusions:

  • Clonotrace offers a powerful approach to leverage lineage barcode information for enhanced cell fate inference.
  • The framework is broadly applicable to various lineage-barcoded single-cell datasets, including T cells in immunotherapy and tumor microenvironments.
  • This method advances the study of cell dynamics, differentiation, and lineage commitment.