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  • The exceptionally photostable green fluorescent protein StayGold has been monomerized in different laboratories, which has generated three unique monomeric variants that will enable new imaging applications.

    • Joachim Goedhart
    • Theodorus W. J. Gadella Jr
    News & Views
  • Diploid assembly is a difficult task that requires several types of genomic sequencing data, including — but not limited to — HiFi reads and parental sequences. Hypo-assembler, an assembly algorithm, uses high quality solid k-mers extracted from Illumina data alongside Nanopore reads to produce a high-quality diploid assembly using only Nanopore and Illumina data.

    Research Briefing
  • We developed a high-content profiling method named vibrational painting (VIBRANT) for single-cell drug response measurements, combining vibrational imaging, multiplexed vibrational probes and machine learning. VIBRANT showed high performance in predicting drug mechanisms of action, discovering novel compounds and assessing drug combinations, demonstrating great promise for phenotypic drug discovery.

    Research Briefing
  • We introduce a biomimetic antigen-presenting system that uses hexapod heterostructures for specific T cell recognition at the single-molecule and single-cell levels. The system enables high-resolution T cell activation, uses magnetic forces to increase immune responses, and offers flexible and precise identification of antigen-specific T cell receptors, aiding the study of T cell recognition and immune cell mechanics.

    Research Briefing
  • Interactions between RNA and RNA-binding proteins (RBPs) define the fate and function of every RNA molecule. We present TREX, or targeted RNase H-mediated extraction of crosslinked RBPs, an efficient and accurate method to unbiasedly reveal the protein interactors of specific regions of RNAs isolated from living cells.

    Research Briefing
  • We established a method to generate complex self-organizing bone marrow-like organoids (BMOs) via concomitant differentiation of human induced pluripotent stem cells. These BMOs consist of hematopoietic cells, stromal niche cells and de novo vascular networks. In addition, they contain multipotent hematopoietic stem and progenitor cells, as well as mesenchymal stem and progenitor cells; they model aspects of the three-dimensional bone marrow architecture and can be used to study developmental and aberrant hematopoiesis.

    Research Briefing
  • We developed Significant Latent Factor Interaction Discovery and Exploration (SLIDE), an interpretable machine learning approach that can infer hidden states (latent factors) underlying biological outcomes. These states capture the complex interplay between factors derived from multiscale, multiomic datasets across biological contexts and scales of resolution.

    Research Briefing
  • We developed Tapioca, an integrative ensemble machine learning-based framework, to accurately predict global protein–protein interaction network dynamics. Tapioca enabled the characterization of host regulation during reactivation from latency of an oncogenic virus. Introducing an interactome homology analysis method, we identified a proviral host factor with broad relevance for herpesviruses.

    Research Briefing
  • sc-SPORT offers a way to probe RNA structure at the single-cell level. It reveals cell-to-cell heterogeneity in RNA folding.

    • Elizabeth A. Jolley
    • Philip C. Bevilacqua
    News & Views
  • We pinpoint PCR artifacts as the primary source of inaccurate quantification in both short- and long-read RNA sequencing, a problem that intensifies with an increase in PCR cycles in both bulk and single-cell sequencing contexts. To overcome this challenge, we engineered a novel unique molecular identifier (UMI) barcode composed of homotrimer nucleotide blocks. This design facilitates accurate quantification of RNA molecules, substantially improving molecular counting.

    Research Briefing
  • We developed a prime editing (PE) strategy by incorporating a 5′–3′ exonuclease activity, which enhanced the efficacy and precision of ≥30-nucleotide DNA insertions without a secondary nick. Our optimization of the PE complex revealed that recruiting the exonuclease via an RNA aptamer outperformed direct protein fusions.

    Research Briefing
  • Intrinsically disordered regions of proteins are prevalent across the kingdoms of life; however, biophysical characterization is expensive, requiring specialized expertise and equipment and time-consuming sample preparation. By combining simulations and deep learning, we have developed a method to predict their average ensemble properties directly from sequence.

    Research Briefing
  • In 1858, the first standard for microscope objectives was established to encourage interchangeable components. Over the following 150 years, standards have evolved to constrain the size of objectives, which limits the parameters of working distance, field of view and resolution. A new design breaks out of this conventional envelope, offering an ultra-long working distance in air and enabling new neuroscience experiments.

    Research Briefing
  • We have developed a framework for the analysis of multi-batch proteome profiling data using isobaric mass tags. Our framework improves quantitative accuracy and increases statistical power by accounting for known sources of variation between batches, thus enabling multiplexed proteome profiling analysis to be performed on large numbers of samples and population cohorts.

    Research Briefing
  • Two studies show that nanopores can identify the 20 proteinogenic amino acids and some of their post-translational modifications. Coupled with an exopeptidase, a bottom-up approach to protein sequencing using nanopores is on the horizon.

    • Andrea Bonini
    • Adina Sauciuc
    • Giovanni Maglia
    News & Views