CRISPR technology: A decade of genome editing is only the beginning

Science, Год журнала: 2023, Номер 379(6629)

Опубликована: Янв. 19, 2023

The advent of clustered regularly interspaced short palindromic repeat (CRISPR) genome editing, coupled with advances in computing and imaging capabilities, has initiated a new era which genetic diseases individual disease susceptibilities are both predictable actionable. Likewise, genes responsible for plant traits can be identified altered quickly, transforming the pace agricultural research breeding. In this Review, we discuss current state CRISPR-mediated manipulation human cells, animals, plants along relevant successes challenges present roadmap future technology.

Язык: Английский

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What is a cell type and how to define it?

Cell, Год журнала: 2022, Номер 185(15), С. 2739 - 2755

Опубликована: Июль 1, 2022

Язык: Английский

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Phase Transitions of Associative Biomacromolecules

Chemical Reviews, Год журнала: 2023, Номер 123(14), С. 8945 - 8987

Опубликована: Март 7, 2023

Multivalent proteins and nucleic acids, collectively referred to as multivalent associative biomacromolecules, provide the driving forces for formation compositional regulation of biomolecular condensates. Here, we review key concepts phase transitions aqueous solutions specifically that include folded domains intrinsically disordered regions. The these systems come under rubric coupled segregative transitions. underlying processes are presented, their relevance condensates is discussed.

Язык: Английский

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Phase-separating RNA-binding proteins form heterogeneous distributions of clusters in subsaturated solutions

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(28)

Опубликована: Июль 5, 2022

Macromolecular phase separation is thought to be one of the processes that drives formation membraneless biomolecular condensates in cells. The dynamics are follow tenets classical nucleation theory, and, therefore, subsaturated solutions should devoid clusters with more than a few molecules. We tested this prediction using vitro biophysical studies characterize phase-separating RNA-binding proteins intrinsically disordered prion-like domains and domains. Surprisingly, direct contradiction expectations from we find characterized by presence heterogeneous distributions clusters. cluster sizes, which dominated small species, shift continuously toward larger sizes as protein concentrations increase approach saturation concentration. As result, many encompass tens hundreds molecules, while less 1% mesoscale species several hundred nanometers diameter. supersaturated strongly coupled via sequence-encoded interactions. also can decoupled solutes well specific sets mutations. Our findings, concordant predictions for associative polymers, implicate an interplay between networks sequence-specific solubility-determining interactions that, respectively, govern above occurs.

Язык: Английский

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CRISPR-based genome editing through the lens of DNA repair

Molecular Cell, Год журнала: 2022, Номер 82(2), С. 348 - 388

Опубликована: Янв. 1, 2022

Язык: Английский

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Trapped Ion Mobility Spectrometry and Parallel Accumulation–Serial Fragmentation in Proteomics

Molecular & Cellular Proteomics, Год журнала: 2021, Номер 20, С. 100138 - 100138

Опубликована: Янв. 1, 2021

Recent advances in efficiency and ease of implementation have rekindled interest ion mobility spectrometry, a technique that separates gas phase ions by their size shape can be hybridized with conventional LC MS. Here, we review the recent development trapped spectrometry (TIMS) coupled to TOF mass analysis. In particular, parallel accumulation–serial fragmentation (PASEF) operation mode offers unique advantages terms sequencing speed sensitivity. Its defining feature is it synchronizes release from TIMS device downstream selection precursors for quadrupole configuration. As are compressed into narrow peaks, number peptide fragment spectra obtained data-dependent or targeted analyses increased an order magnitude without compromising Taking advantage correlation between mass, PASEF principle also multiplies data-independent acquisition. This makes technology well suited rapid proteome profiling, increasingly important attribute clinical proteomics, as ultrasensitive measurements down single cells. The accuracy enable precise collisional cross section values at scale more than million data points neural networks capable predicting them based only on sequences. Peptide differ isobaric sequences positional isomers post-translational modifications. additional information may leveraged real time direct acquisition postprocessing increase confidence identifications. These developments make powerful expandable platform proteomics beyond.

Язык: Английский

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The phenotypic landscape of essential human genes

Cell, Год журнала: 2022, Номер 185(24), С. 4634 - 4653.e22

Опубликована: Ноя. 1, 2022

Язык: Английский

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Integrated intracellular organization and its variations in human iPS cells

Nature, Год журнала: 2023, Номер 613(7943), С. 345 - 354

Опубликована: Янв. 4, 2023

Understanding how a subset of expressed genes dictates cellular phenotype is considerable challenge owing to the large numbers molecules involved, their combinatorics and plethora behaviours that they determine

Язык: Английский

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Self-supervised deep learning encodes high-resolution features of protein subcellular localization

Nature Methods, Год журнала: 2022, Номер 19(8), С. 995 - 1003

Опубликована: Июль 25, 2022

Abstract Explaining the diversity and complexity of protein localization is essential to fully understand cellular architecture. Here we present cytoself, a deep-learning approach for self-supervised profiling clustering. Cytoself leverages training scheme that does not require preexisting knowledge, categories or annotations. Training cytoself on images 1,311 endogenously labeled proteins from OpenCell database reveals highly resolved atlas recapitulates major scales organization, coarse classes, such as nuclear cytoplasmic, subtle signatures individual complexes. We quantitatively validate cytoself’s ability cluster into organelles complexes, showing outperforms previous approaches. Moreover, better inner workings our model, dissect emergent features which clustering derived, interpret them in context fluorescence images, analyze performance contributions each component approach.

Язык: Английский

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Spatial omics technologies at multimodal and single cell/subcellular level

Genome biology, Год журнала: 2022, Номер 23(1)

Опубликована: Дек. 13, 2022

Abstract Spatial omics technologies enable a deeper understanding of cellular organizations and interactions within tissue interest. These assays can identify specific compartments or regions in with differential transcript protein abundance, delineate their interactions, complement other methods defining phenotypes. A variety spatial methodologies are being developed commercialized; however, these techniques differ resolution, multiplexing capability, scale/throughput, coverage. Here, we review the current prospective landscape single cell to subcellular resolution analysis tools provide comprehensive picture for both research clinical applications.

Язык: Английский

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