A5069819433- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Radiomics and Machine Learning in Medical Imaging
- Advanced biosensing and bioanalysis techniques
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Genome Rearrangement Algorithms
- Chromosomal and Genetic Variations
- Cancer Immunotherapy and Biomarkers
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
Stanford University
2024
Whitehead Institute for Biomedical Research
2021-2022
University of California, Berkeley
2021-2022
University of California, San Francisco
2021-2022
QB3
2021-2022
Howard Hughes Medical Institute
2021
Massachusetts Institute of Technology
2021
Following cancer through the body The heterogeneity of mammalian tumors has been well documented, but it remains unknown how differences between individual cells lead to metastasis and spread throughout body. Quinn et al. created a Cas9-based lineage tracer used single-cell sequencing generate phylogenies follow movement metastatic human implanted in lung mouse xenograph model. Using this model, they found that within same cell line, exhibited diverse phenotypes. These subclones differential...
The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while different chromosomes assort independently
<p>sgRNA, primer, and probe sequences.</p>
<p>Supplementary Figure S1. PCR detects circle junctions for all MYC ecDNA guide pairs tested. Supplementary S2. Hi-C contact frequency, sgRNA indel efficiency, and circularization rates in Hap1 K562 cells. S3. scar formation frequencies initial CRISPR-C screen. S4. Junction type microhomology frequency Hap1, K562, FTE5 organoids. S5. Impact of different MH thresholds on across loci cell types insertion length distribution at TCGA junctions. S6. ATR inhibition has no impact DHFR or...
<div>Abstract<p>Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms limited. In this study, we couple CRISPR-based method for induction with extensive characterization newly formed ecDNAs to examine their biogenesis. We find that circularization efficient, irrespective 3D genome context, the formation 800 kb, 1 Mb, and 1.8 Mb reaching or exceeding 15%. show nonhomologous end joining...
Extrachromosomal DNA (ecDNA) amplifications are prevalent drivers of human cancers. We show that ecDNAs exhibit elevated structural variants leading to gene fusions produce oncogene fusion transcripts. The long noncoding RNA (lncRNA) PVT1 is the most recurrent variant across cancer genomes, with PVT1-MYC arising frequently on ecDNA. exon 1 predominant 5' partner fused MYC or other oncogenes 3' end. Mechanistic studies demonstrate confers enhanced stability for transcripts, which requires...
Abstract Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms limited. In this study, we couple CRISPR-based method for induction with extensive characterization newly formed ecDNAs to examine their biogenesis. We find that circularization efficient, irrespective 3D genome context, the formation 800 kb, 1 Mb, and 1.8 Mb reaching or exceeding 15%. show nonhomologous end joining microhomology-mediated both...
Extrachromosomal DNA (ecDNA) is a central mechanism for focal oncogene amplification in cancer, occurring ∼15% of early-stage cancers and ∼30% late-stage cancers. ecDNAs drive tumor formation, evolution, drug resistance by dynamically modulating copy number rewiring gene-regulatory networks. Elucidating the genomic architecture ecDNA amplifications critical understanding pathology developing more effective therapies. Paired-end short-read (Illumina) sequencing mapping have been utilized to...
ABSTRACT Tumor progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumors can provide crucial insights into how intrinsic changes within extrinsic alterations in microenvironment cooperate to drive different stages tumor progression. Here, we integrate high-resolution spatial transcriptomics evolving lineage tracing technologies elucidate expansion, plasticity, metastasis co-evolve with...
A bstract Novel experimental assays now simultaneously measure lineage relationships and transcriptomic states from single cells, thanks to CRISPR/Cas9-based genome engineering. These multimodal measurements allow researchers not only build comprehensive phylogenetic models relating all cells but also infer determinants of consequential subclonal behavior. The gene expression data, however, is limited that are currently present (“leaves” the phylogeny). As a consequence, cannot form...
Recent advances in CRISPR-Cas9 engineering and single-cell assays have enabled the simultaneous measurement of transcriptomic phylogenetic profiles. However, there are few computational tools enabling users to integrate derive insight from a joint analysis these two modalities. Here, we describe "PhyloVision": an open-source software for interactively exploring data both modalities identifying interpreting heritable gene modules whose concerted expression associated with relationships....
SUMMARY Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth, expansion to neighboring distal tissues, therapeutic resistance. The study phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout mouse model Kras;Trp53 (KP)-driven lung adenocarcinoma which enabled us track tumor from single...
CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylo- genies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is challenging. In work, we derive a algorithm theoret- ical using Neighbor-Joining (NJ) on distances that are moment-matched to estimate true tree distances. We develop series tools analyze and prove its guarantees. When parameters data generating process known...
SUMMARY Recent advances in CRISPR-Cas9 engineering and single-cell assays have enabled the simultaneous measurement of transcriptomic phylogenetic profiles. However, there are few computational tools enabling users to integrate derive insight from a joint analysis these two modalities. Here, we describe PhyloVision: an open source software for interactively exploring data both modalities identifying interpreting heritable gene modules whose concerted expression associated with relationships....