Martin J. Aryee
Broad Institute
Publications 106
#1Yannick Berker (DKFZ: German Cancer Research Center)H-Index: 8
#2Lindsey A. Vandergrift (Harvard University)H-Index: 4
Last.Leo K. Cheng (Harvard University)H-Index: 37
view all 13 authors...
Low-dose CT has shown promise in detecting early stage lung cancer. However, concerns about the adverse health effects of radiation and high cost prevent its use as a population-wide screening tool. Effective and feasible screening methods to triage suspicious patients to CT are needed. We investigated human lung cancer metabolomics from 93 paired tissue-serum samples with magnetic resonance spectroscopy and identified tissue and serum metabolomic markers that can differentiate cancer types and ...
#1Divy Kangeyan (Broad Institute)H-Index: 1
#2Andrew Dunford (Broad Institute)H-Index: 5
Last.Martin J. AryeeH-Index: 34
view all 7 authors...
Background Bisulfite sequencing allows base-pair resolution profiling of DNA methylation and has recently been adapted for use in single-cells. Analyzing these data, including making comparisons with existing data, remains challenging due to the scale of the data and differences in preprocessing methods between published datasets.
1 CitationsSource
#1Killian S. Hanlon (Harvard University)H-Index: 1
#2Benjamin P. Kleinstiver (Harvard University)H-Index: 15
Last.Bence György (Harvard University)H-Index: 20
view all 19 authors...
Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels of AAV integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide AAV mapping in mouse brain shows no overall increase of AAV integration ...
#1Huidong ChenH-Index: 5
#2L Albergante (French Institute of Health and Medical Research)H-Index: 1
Last.Luca Pinello (Broad Institute)H-Index: 22
view all 15 authors...
Single-cell transcriptomic assays have enabled the de novo reconstruction of lineage differentiation trajectories, along with the characterization of cellular heterogeneity and state transitions. Several methods have been developed for reconstructing developmental trajectories from single-cell transcriptomic data, but efforts on analyzing single-cell epigenomic data and on trajectory visualization remain limited. Here we present STREAM, an interactive pipeline capable of disentangling and visual...
12 CitationsSource
#1Julian Grünewald (Harvard University)H-Index: 2
#2Ronghao Zhou (Harvard University)H-Index: 2
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 7 authors...
Cytosine or adenine base editors (CBEs or ABEs) can introduce specific DNA C-to-T or A-to-G alterations1–4. However, we recently demonstrated that they can also induce transcriptome-wide guide-RNA-independent editing of RNA bases5, and created selective curbing of unwanted RNA editing (SECURE)-BE3 variants that have reduced unwanted RNA-editing activity5. Here we describe structure-guided engineering of SECURE-ABE variants with reduced off-target RNA-editing activity and comparable on-target DNA...
#1Caleb A. Lareau (Broad Institute)H-Index: 14
#2Fabiana M. Duarte (Broad Institute)H-Index: 5
Last.Jason D. Buenrostro (Broad Institute)H-Index: 23
view all 11 authors...
Recent technical advancements have facilitated the mapping of epigenomes at single-cell resolution; however, the throughput and quality of these methods have limited their widespread adoption. Here we describe a high-quality (105 nuclear fragments per cell) droplet-microfluidics-based method for single-cell profiling of chromatin accessibility. We use this approach, named ‘droplet single-cell assay for transposase-accessible chromatin using sequencing’ (dscATAC-seq), to assay 46,653 cells for th...
3 CitationsSource
#1Matteo Ligorio (Harvard University)H-Index: 10
#2Srinjoy Sil (Harvard University)H-Index: 5
Last.David T. Ting (Harvard University)H-Index: 27
view all 48 authors...
Summary Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenc...
10 CitationsSource
#1Leif S. Ludwig (Broad Institute)H-Index: 10
#2Caleb A. LareauH-Index: 14
Last.Vijay G. Sankaran (Broad Institute)H-Index: 33
view all 13 authors...
Summary Human erythropoiesis serves as a paradigm of physiologic cellular differentiation. This process is also of considerable interest for better understanding anemias and identifying new therapies. Here, we apply deep transcriptomic and accessible chromatin profiling to characterize a faithful ex vivo human erythroid differentiation system from hematopoietic stem and progenitor cells. We reveal stage-specific transcriptional states and chromatin accessibility during various stages of erythrop...
4 CitationsSource
#1Julian Grünewald (Harvard University)H-Index: 2
#2Ronghao Zhou (Harvard University)H-Index: 2
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 7 authors...
Abstract CRISPR-guided DNA base editors enable the efficient installation of targeted single-nucleotide changes. Cytosine or adenine base editors (CBEs or ABEs), which are fusions of cytidine or adenosine deaminases to CRISPR-Cas nickases, can efficiently induce DNA C-to-T or A-to-G alterations in DNA, respectively1-4. We recently demonstrated that both the widely used CBE BE3 (harboring a rat APOBEC1 cytidine deaminase) and the optimized ABEmax editor can induce tens of thousands of guide RNA-i...
3 CitationsSource
#1Julian GrünewaldH-Index: 2
#2Ronghao Zhou (Harvard University)H-Index: 2
Last.J. Keith JoungH-Index: 62
view all 7 authors...
CRISPR-Cas base editor technology enables targeted nucleotide alterations and is being rapidly deployed for research and potential therapeutic applications1,2. The most widely used base editors induce DNA cytosine (C) deamination with rat APOBEC1 (rAPOBEC1) enzyme, which is targeted by a linked Cas protein-guide RNA (gRNA) complex3,4. Previous studies of cytosine base editor (CBE) specificity have identified off-target DNA edits in human cells5,6. Here we show that a CBE with rAPOBEC1 can cause ...
27 CitationsSource