# Cellular Phylogenetics and Evolution

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2022 · $336,813

## Abstract

Project Summary/Abstract
Molecular evolution and genomics research has entered an exciting phase with the advent of sequencing
techniques, enabling us to profile genome variation from hundreds of cells from an individual. Now, evolutionary
patterns and processes can be revealed at the highest cellular resolution. However, the state-of-the-art
phylogeny reconstruction methods perform poorly for cellular sequencing data because the number of genetic
variants is small due to a low mutation rate and short time span. Cellular sequence alignments are frequently
tall, i.e., a small number of variants (columns) and a large number of sequences (cells, rows). A common feature
of these tall datasets is the presence of sequencing error due to technical challenges associated with single-cell
sequencing. Even small sequencing errors cause inferred cellular phylogenies to become unreliable and produce
erroneous downstream biological inferences. We will develop innovative methods for molecular evolutionary and
phylogenetic analysis of tall data for studying somatic and pathogen evolution. Specifically, our aims will be to
(a) develop a mutation ordering and phylogeny estimation (MOPE) framework to infer tall data phylogenies
accurately and (b) integrate MOPE with traditional phylogenetic methods to further increase the accuracy of
evolutionary inferences. We will also (c) develop a library of software for high-throughput analysis of tall data.
Ultimately, the proposed software and research developments will advance molecular evolution and genomics,
bioinformatics, and biomedicine. New software and its source code will be made available free for research,
education, and training.

## Key facts

- **NIH application ID:** 10418915
- **Project number:** 1R01LM014005-01
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Sayaka Miura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $336,813
- **Award type:** 1
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418915

## Citation

> US National Institutes of Health, RePORTER application 10418915, Cellular Phylogenetics and Evolution (1R01LM014005-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10418915. Licensed CC0.

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