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Single-cell nanobody-tethered transposition followed by sequencing (scNTT-seq) is a new assay that measures the genome-wide presence of multiple histone modifications and protein–DNA binding sites at single-cell resolution. scNTT-seq generates high-resolution multimodal maps of chromatin states with high accuracy and sensitivity.
Nanobody–Tn5 transposase fusion proteins enable detection of two histone marks and open chromatin regions at the same time, with single-cell resolution.
We developed a computational method based on Strand-seq that combines nucleosome occupancy and structural variation analysis in single cells to identify the functional effects of somatic structural variants in leukemia. The method revealed the molecular consequences of somatic driver mutations and informed specific therapeutic targeting of a chromothriptic leukemic subclone.
We developed a wireless smart bandage with sensors that can detect the condition of a wound and stimulators that can deliver electric cues. Application of our device on wounds in mouse models reduced infection and accelerated wound healing.
The global microbiota contains an enormous, previously inaccessible reservoir of biodiversity that can now be captured as large DNA fragments in clone libraries. To mine cloned biodiversity more effectively, we developed a CRISPR-interference-based counter-selection interruption circuit for the high-throughput retrieval of desired clones within complex libraries.
Development is orchestrated in part by myriad chromatin-associated proteins that decorate the genome and physically coordinate in ways that are often unclear. An epigenomics technique called MulTI-Tag maps the genomic locations of different chromatin proteins in the same individual cells, helping to unveil their interactions.
The ability to target the majority of human transcription factors remains an as yet unachieved goal in chemical biology and medicine. We developed a modular, synthetic transcriptional repressor platform that recapitulates the DNA-binding properties of native basic helix-loop-helix (bHLH) domains and can block the DNA-binding functions of an important oncogenic transcription factor target, MYC.
Spatial total RNA-sequencing (STRS) combines in situ polyadenylation with existing spatial transcriptomics technologies to enable a broader view of the transcriptome in tissues. We use STRS to spatially map coding, noncoding and nonhost RNAs in models of skeletal muscle regeneration and viral myocarditis.
Cells differentiate to their final fates through sequential epigenetic and transcriptional changes. A mathematical model fit on multi-omic single-cell data yields insights into the temporal relationships between chromatin accessibility and gene expression during cell differentiation.
Post-translational modifications (PTMs) alter the structure, properties and functions of proteins in all aspects of biology. A new computational pipeline, termed protein modification integrated search engine (PROMISE), reveals the impact these modifications might have on the presentation of cancer antigens to T cells.
We integrated the pre-characterized physical model of super-resolution (SR) microscopy into a deep neural network to guide the denoising of raw images for high-quality SR image reconstruction. This approach enabled us to investigate a wide variety of fragile and rapidly evolving bioprocesses at ultrahigh spatiotemporal resolution over extended imaging times.
Accurate identification and effective removal of unwanted variation is essential to derive meaningful biological results from large and complex RNA-seq studies. Technical replicates together with negative and positive control genes are key tools for carrying out this task. We show how to proceed when technical replicates are unavailable.
The addition of Cas9 target sequences to long single-stranded DNAs, combined with cocktails of small molecules to boost homology-directed repair, leads to marked enhancement of non-viral knock-in efficiency and yield in primary human T cells and other hematopoietic cell types.