A5019447793- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- Neutropenia and Cancer Infections
- Genomics and Phylogenetic Studies
- Acute Myeloid Leukemia Research
- Bacterial Identification and Susceptibility Testing
- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Mycobacterium research and diagnosis
- Chronic Myeloid Leukemia Treatments
- Prenatal Screening and Diagnostics
- Plant Disease Resistance and Genetics
- Circular RNAs in diseases
- MicroRNA in disease regulation
- Hematopoietic Stem Cell Transplantation
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Advanced biosensing and bioanalysis techniques
Chan Zuckerberg Initiative (United States)
2020-2024
Stanford University
2011-2024
Stanford Medicine
2023
St. Jude Children's Research Hospital
2016-2022
University of Tennessee Health Science Center
2019
Palo Alto University
2011-2016
Howard Hughes Medical Institute
2014
Cancer Prevention Institute of California
2013
Stanford Cancer Institute
2013
UCLA Medical Center
2010
Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by genomic sequence. By deep sequencing of RNA from a variety normal and malignant cells, we found transcripts many genes in which exons were arranged non-canonical order. Statistical estimates biochemical assays provided strong evidence substantial fraction hundreds circular RNAs. Our results suggest mode splicing, resulting isoform, is general feature gene expression program cells.
Abstract Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated cells from diverse lineages. Pan-cancer analyses have been performed for adult 1,2,3,4 but not paediatric cancers, which commonly occur developing mesodermic rather than epithelial tissues 5 . Here we present a study somatic alterations, including single nucleotide variants, small insertions or...
Significance A better understanding of intratumor heterogeneity is required to more fully dissect the events which mediate cancer formation and treatment resistance. We used a novel experimental computational single-cell sequencing approach directly measure clonal structures childhood ALL samples at diagnosis. This enabled us determine mutation segregation patterns within single sample reconstruct tumor’s with rigorously validated quantitative analysis. then identified features each leukemia...
Significance Circulating cell-free RNA in the blood provides a potential window into health, phenotype, and developmental programs of variety human organs. We used high-throughput methods analysis such as microarrays next-generation sequencing to characterize global landscape circulating subjects. By focusing on tissue-specific genes, we were able identify relative contributions these tissues monitor changes during tissue development neurodegenerative disease states.
Single-cell sequencing is emerging as an important tool for studies of genomic heterogeneity. Whole genome amplification (WGA) a key step in single-cell workflows and multitude methods have been introduced. Here, we compare three state-of-the-art on both bulk samples E. coli DNA: Multiple Displacement Amplification (MDA), Annealing Looping Based Cycles (MALBAC), the PicoPLEX WGA kit (NEB-WGA). We considered effects reaction gain coverage uniformity, error rates level background...
The cerebellum develops from a restricted number of cell types that precisely organize to form the circuitry controls sensory-motor coordination and some higher-order cognitive processes. To acquire an enhanced understanding molecular processes mediate cerebellar development, we performed single-cell RNA-sequencing 39,245 murine cells at twelve critical developmental time points. Using recognized lineage markers, confirmed data accurately recapitulate development. We then followed distinct...
Significance Primary template-directed amplification (PTA) is a major improvement in whole genome amplification, which required to study intratissue cellular evolution. As presented the manuscript, PTA produces significantly improved and reproducible sequencing coverage variant detection from single of cell. Applications measuring genetic diversity cells with manuscript include examining acquisition changes during normal development aging, consequences specific perturbations such as editing,...
Bloodstream infection (BSI) is a common, life-threatening complication of treatment for cancer. Predicting BSI before onset clinical symptoms would enable preemptive therapy, but there no reliable screening test.
In vivo direct conversion of differentiated cells holds promise for regenerative medicine; however, improving the efficiency and producing functional target remain challenging. Ectopic Atoh1 expression in non-sensory supporting (SCs) mouse cochleae induces their partial to hair (HCs) at low efficiency. Here, we performed single-cell RNA sequencing whole sensory epithelia harvested multiple time points after conditional overexpression Atoh1. Pseudotemporal ordering revealed that converted HCs...
Significance Most genetic studies and clinical testing do not look for the possibility of mosaic variation. The form long-QT syndrome (LQTS) can result in life-threatening arrhythmias, but 30% patients have a diagnosis. We performed deep characterization variant an infant with perinatal LQTS developed computational model showing how abnormal cellular repolarization only 8% heart cells may cause arrhythmia. Finally we looked at prevalence mosaicism among LQTS; population 7,500 individuals...
Intra-tumor heterogeneity stems from genetic, epigenetic, functional, and environmental differences among tumor cells. A major source of genetic comes DNA sequence and/or whole chromosome focal copy number variations (CNVs). Whole CNVs are caused by chromosomal instability (CIN) that is defined a persistently high rate mis-segregation. Accordingly, CIN causes constantly changing karyotypes result in extensive cell-to-cell heterogeneity. How the influences gene expression individual cells...
Over 80% of children with acute lymphoblastic leukemia (pALL) can be cured by treating them multiple chemotherapeutic agents administered over several years, whereas pALL is incurable 1-3 medications, suggesting significant variation in drug susceptibility across clonal populations. While bulk sequencing studies indicate that cells contain relatively few genetic variants compared to other cancers, the true extent diversity at single-cell level remains unknown. Here, we used three...
The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. same developmental makes it difficult identify specific markers that discern between intraembryonic versus YS-origin using a lineage trace approach. Additionally, highly migratory nature blood cells and inability pre-circulatory (i.e., 5-7 somite pairs (sp))...
Abstract Primary template-directed amplification (PTA) is an improved technique for single-cell DNA sequencing. We generated whole-genome analysis of 76 single neurons and developed SCAN2, a computational method to accurately identify both clonal non-clonal somatic (i.e., limited neuron) nucleotide variants (SNVs) small insertions deletions (indels) using PTA data. Our confirms increase in mutation with age, but revises estimates the rate this accumulation be 15 SNVs per year. also artifacts...
Circular RNAs comprise a poorly understood new class of noncoding RNA. In this study, we used combination targeted deletion, high-resolution splicing detection, and single-cell sequencing to deeply probe ASXL1 circular splicing. We found that efficient required the canonical transcriptional start site inverted AluSx elements. Sequencing-based interrogation isoforms after overexpression identified promiscuous linear between all exons, with two most abundant non-canonical products skipping...
Summary The broad application of single-cell RNA sequencing has revealed transcriptional cell state heterogeneity across diverse healthy and malignant somatic tissues. Recent advances in lineage tracing technologies have further enabled the simultaneous capture along with cellular ancestry thus enabling study evolution at an unprecedented resolution; however, new analytical approaches are needed to fully harness these data. Here we introduce PATH (Phylogenetic Analysis Transcriptional...
Abstract Background Mixed phenotype acute leukemia (MPAL), a rare subgroup of characterized by blast cells with myeloid and lymphoid lineage features, is difficult to diagnose treat. A better characterization MPAL essential understand the subtype heterogeneity how it compares (AML) lymphoblastic (ALL). Therefore, we performed single-cell RNA sequencing (scRNAseq) on pediatric bone marrow (BM) samples develop granular map blasts microenvironment landscape. Methods We analyzed over 40,000 from...