Sequencing articles within Nature Communications

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  • Article
    | Open Access

    Compact RNA structural motifs control many aspects of gene expression, but methods for their identification are lacking. Here the authors present a sequencing-based terbium probing approach to detect complex 3D structural elements, which can be used to pinpoint potential riboregulatory elements.

    • Shivali Patel
    • , Alec N. Sexton
    •  & Anna Marie Pyle

  • Article
    | Open Access

    Village cultures, where multiple stem cell lines are cultured in a single dish, provide an elegant solution for population-scale studies. Here, authors show the utility of village models – showing that expression heterogeneity is largely a result of line-specific effects and not village cultures.

    • Drew R. Neavin
    • , Angela M. Steinmann
    •  & Joseph E. Powell

  • Article
    | Open Access

    Protein sequencing is one of the key aims of the nanopore field. Working toward this goal, here the authors report the direct identification of single amino acids in MoS2 nanopores with sub-1 Dalton resolution, as well as the discrimination of the amino acid isomers and amino acid phosphorylation.

    • Fushi Wang
    • , Chunxiao Zhao
    •  & Jiandong Feng

  • Article
    | Open Access

    Single cell sequencing can be used to better characterize immune cell progenitors. Here the authors characterize CLEC12Ahi pre-basophils downstream of pre-basophil and mast cell progenitors (pre-BMPs) but upstream of mature basophils and this population includes basophil progenitors (BaPs).

    • Kensuke Miyake
    • , Junya Ito
    •  & Hajime Karasuyama

  • Article
    | Open Access

    The contribution of cell-extrinsic factors during cellular reprogramming to human induced pluripotent stem cells has long been overlooked. Here, the authors show functional protein communication between reprogramming intermediates and the re-shaping of a permissive extracellular environment.

    • Francesco Panariello
    • , Onelia Gagliano
    •  & Nicola Elvassore

  • Article
    | Open Access

    Long-read single-cell RNA isoform sequencing can elucidate the intricate landscape of alternative RNA splicing in individual cells, but it suffers from a low read throughput. Here, the authors develop circular consensus sequencing methods to allow high-throughput and high-accuracy single-cell RNA isoform sequencing.

    • Zhuo-Xing Shi
    • , Zhi-Chao Chen
    •  & Yi-Zhi Liu

  • Article
    | Open Access

    Single-nucleus RNA-seq was used to profile 11 retinas with varying stages of age-related macular degeneration and 6 control retinas. The authors identified shared glial states across neurodegeneration, indicating that the retina provides a human system for investigating therapeutic approaches in neurodegeneration.

    • Manik Kuchroo
    • , Marcello DiStasio
    •  & Brian P. Hafler

  • Article
    | Open Access

    Methods to reanalyze scRNA-seq data in a spatial perspective are vital but lacking. Here, the authors develop scSpace, an integrative method that uses ST data as spatial reference to reconstruct the pseudo-space of scRNA-seq data and identify spatially variable cell subpopulations, providing insights into spatial heterogeneity from scRNA-seq data.

    • Jingyang Qian
    • , Jie Liao
    •  & Xiaohui Fan

  • Article
    | Open Access

    Efforts to convert aptamers into molecular switches using rational design are often unsuccessful. Here the authors describe a massively parallel screening-based strategy whereby millions of potential aptamer switches are synthesised, sequenced and screened directly on a flow-cell.

    • Alex M. Yoshikawa
    • , Alexandra E. Rangel
    •  & H. Tom Soh

  • Article
    | Open Access

    Stromal cells are essential for intestinal homeostasis. Here the authors describe the phenotype, transcriptional profile and location of stromal cell subsets in the adult murine small intestine and colon lamina propria and demonstrate that these cells derive from Gli1+ precursors present in embryonic day 12.5 intestine.

    • Simone Isling Pærregaard
    • , Line Wulff
    •  & William W. Agace

  • Article
    | Open Access

    Chemotherapy priming sensitizes triple-negative breast cancers to immune checkpoint blockade. However, immune suppressive myeloid cells may impede its optimal effect. Here authors characterise the immune suppressive myeloid cells via single-cell analyses of immune cells from low dose chemotherapy treated breast tumours and identify STAT1 signalling as a regulator for immune suppressive state.

    • Bhavana Palakurthi
    • , Shaneann R. Fross
    •  & Siyuan Zhang

  • Article
    | Open Access

    Liver cirrhosis is characterised by extensive fibrosis of the liver, and understanding the underpinning immunological processes is important in designing intervention. Here authors show that Mucosal-Associated Invariant T cells are instrumental to controlling the balance between profibrogenic and restorative macrophages and inhibiting their activation might reverse liver fibrosis.

    • Morgane Mabire
    • , Pushpa Hegde
    •  & Sophie Lotersztajn

  • Article
    | Open Access

    Different muscle cell types account for specific abilities in animals, yet how their diversification arose remains unclear. Here, the authors show that gene duplications of bHLH transcription factors and effector genes contributed to the diversification of muscle cell types in the sea anemone Nematostella.

    • Alison G. Cole
    • , Stefan M. Jahnel
    •  & Ulrich Technau

  • Article
    | Open Access

    Examining the spatially resolved transcriptome of tissue sections promises advances in biomedical research. Here, the authors present xDBiT, a versatile, microfluidics-based approach to cost-effectively measure the spatial transcriptome of multiple tissue sections in parallel.

    • Johannes Wirth
    • , Nina Huber
    •  & Matthias Meier

  • Article
    | Open Access

    The intestine is an important immunological organ in embryonic life, preparing the infant for the microbial colonization following birth. Here authors show that between gestational weeks 14 and 22, the human foetal intestine is first populated by myeloid and innate lymphoid cells, followed by the development of lymphoid cells and a wider range of proliferation-capable immune cell types.

    • Nannan Guo
    • , Na Li
    •  & Frits Koning

  • Article
    | Open Access

    Cellular plasticity is a core biological process; however, observing diversity in non-genetic inheritance and the resulting phenotypic outputs, is challenging. Here the authors develop a non-genetically based tracing technology which can be used to reveal lineage-linked transcriptome plasticity.

    • Yelyzaveta Shlyakhtina
    • , Bianca Bloechl
    •  & Maximiliano M. Portal

  • Article
    | Open Access

    Head and neck squamous cell carcinomas (HNSCCs) undergo a stepwise progression from normal tissues. In order to better understand the molecular mechanisms behind such progression, here the authors profile HNSCC tumors at different stages using single-cell RNA-seq, and observe the role of interactions with the tumor microenvironment.

    • Ji-Hye Choi
    • , Bok-Soon Lee
    •  & Chul-Ho Kim

  • Article
    | Open Access

    Implementing high-throughput single-cell DNA sequencing for the study of solid tumours has been challenging. Here, the authors present an optimised approach for snap-frozen tissue single nuclei extraction and DNA sequencing, which can be applied to study pancreatic ductal adenocarcinoma evolution and heterogeneity.

    • Haochen Zhang
    • , Elias-Ramzey Karnoub
    •  & Christine A. Iacobuzio-Donahue

  • Article
    | Open Access

    The immune suppressive tumour microenvironment drives recurrence and metastatic disease in prostate cancer. Here authors provide a detailed analysis of the microenvironment via single cell RNA sequencing and high-resolution spatial transcriptomics to identify tumour-dependent changes compared to healthy tissue.

    • Taghreed Hirz
    • , Shenglin Mei
    •  & David B. Sykes

  • Article
    | Open Access

    Spatial transcriptomics relies on RNA quality, which is variable and dependent on sample handling, storage, and/or intrinsic factors. Here, authors present a genome-wide spatial gene expression profiling method called RNA Rescue Spatial Transcriptomics (RRST), designed for the analysis of moderate to low quality fresh frozen tissue samples and demonstrate its robustness on 7 different tissue types.

    • Reza Mirzazadeh
    • , Zaneta Andrusivova
    •  & Joakim Lundeberg

  • Article
    | Open Access

    Mesenchymal-epithelial crosstalk plays a key role in gut development and stem cell homeostasis, though underlying mechanisms are still unclear. Here, the authors demonstrate that mesenchymal Polycomb Repressive Complex 2 controls niche signals for gut epithelial fate and growth.

    • Ryan J. Smith
    • , Minggao Liang
    •  & Tae-Hee Kim

  • Article
    | Open Access

    Single-cell genomics has expanded to measure diverse molecular modalities within the same cell. Here the authors provide a computational framework called scTriangulate to integrate cluster annotations from diverse independent sources, algorithms, and modalities to define statistically stable populations.

    • Guangyuan Li
    • , Baobao Song
    •  & Nathan Salomonis

  • Article
    | Open Access

    A major challenge in analyzing scRNA-seq data arises from challenges related to dimensionality and the prevalence of dropout events. Here the authors develop a deep graph learning method called scMGCA based on a graph-embedding autoencoder that simultaneously learns cell-cell topology representation and cluster assignments, outperforming other state-of-the-art models across multiple platforms.

    • Zhuohan Yu
    • , Yanchi Su
    •  & Xiangtao Li

  • Article
    | Open Access

    Pseudouridine (psi) is an RNA modification that can affect its physiology, including increased half-life. Here the authors identify sites of psi modification in the human transcriptome using direct RNA sequencing and provide a “ground truth” list of psi sites, sites of high psi occupancy, and transcripts that may be modified at multiple sites.

    • Sepideh Tavakoli
    • , Mohammad Nabizadeh
    •  & Sara H. Rouhanifard

  • Article
    | Open Access

    Alveolar macrophages represent a cell type that is physiologic to the lung immune landscape, however, it is not known whether they play an active role to maintain the tumour immune microenvironment. Here authors show by single cell RNA sequencing and functional experiments, that intra-tumour alveolar macrophages are phenotypically and transcriptionally different from the healthy ones, and likely play an aetio-pathologic role in tumorigenesis.

    • Seiji Taniguchi
    • , Takahiro Matsui
    •  & Masaru Ishii

  • Article
    | Open Access

    Li-Fraumeni syndrome (LFS) is associated with pathogenic germline TP53 variants and predisposes patients to cancer; understanding the evolution and drivers of LFS-related tumours remains crucial. Here, the authors analyse 22 LFS tumours using whole-genome sequencing and reconstruct the evolution and timing of somatic driver alterations.

    • Nicholas Light
    • , Mehdi Layeghifard
    •  & Adam Shlien

  • Article
    | Open Access

    The interplay between histone modifications and DNA methylation plays a crucial role in establishing and maintaining the epigenomic landscape. Here, the authors develop a nanopore sequencing based method for mapping histone modifications and DNA methylation from native, long, single DNA molecules.

    • Xue Yue
    • , Zhiyuan Xie
    •  & Yimeng Yin

  • Article
    | Open Access

    Cytotoxic T lymphocytes play important roles in the anti-viral immune response in COVID-19, and it is important to know how they contribute to disease outcome. Authors here identify a dominant SARS-CoV-2 M protein epitope, M198–206, and show that M198–206-specific cytotoxic T cells from convalescent patients with severe disease harbour a gene expression pattern indicative of poor functionality.

    • Hideki Ogura
    • , Jin Gohda
    •  & Satoshi Ishido

  • Article
    | Open Access

    Despite the importance of DNA methylation, accessible and high-throughput methods to profile methylation at the single-cell level are lacking. Here, the authors present sciMETv2, a high-throughput workflow that provides high-quality single-cell methylomes in a robust and simple workflow.

    • Ruth V. Nichols
    • , Brendan L. O’Connell
    •  & Andrew C. Adey

  • Article
    | Open Access

    Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

    • Marsha M. Wheeler
    • , Adrienne M. Stilp
    •  & Alex P. Reiner

  • Article
    | Open Access

    Low-dose interleukin-2 is showing promise in the treatment of several autoimmune inflammatory diseases. Here authors map the trajectory of cellular and transcriptional changes in type 1 diabetes patients receiving an interval dosing interleukin-2 regimen, which shows an anti-inflammatory gene expression signature shared by all immune cell types analysed, persisting for at least a month after ending treatment.

    • Jia-Yuan Zhang
    • , Fiona Hamey
    •  & Ricardo C. Ferreira

  • Article
    | Open Access

    Recovering dropout-affected gene expression values is a challenging problem in bioinformatics. Here, the authors propose a data-driven framework, that first learns the underlying data distribution and then recovers the expression values by imposing a self-consistency on the expression matrix.

    • Md Tauhidul Islam
    • , Jen-Yeu Wang
    •  & Lei Xing

  • Article
    | Open Access

    The 1+ million publicly-available human –omics samples currently remain acutely underused. Here the authors present an approach combining natural language processing and machine learning to infer the source tissue of public genomics samples based on their plain text descriptions, making these samples easy to discover and reuse.

    • Nathaniel T. Hawkins
    • , Marc Maldaver
    •  & Arjun Krishnan

  • Article
    | Open Access

    Traditional bulk sequencing data lack information about cell-type-specific gene expression. Here, the authors develop a Tissue-AdaPtive autoEncoder (TAPE), a deep learning method connecting bulk RNA-seq and single-cell RNA-seq, and apply it to analyze the cell type fractions and cell-type-specific gene expression in clinical data.

    • Yanshuo Chen
    • , Yixuan Wang
    •  & Yu Li

  • Article
    | Open Access

    Carriers of pathogenic BRCA1/2 variants have a higher risk of breast and ovarian cancers, which recur frequently. Here, the authors sequence primary and recurrent tumours of BRCA1/2 mutation carriers, finding PARP1 amplifications, differential BRCA2 isoform usage, and discordant loss of heterozygosity that are associated with recurrence.

    • Jennifer B. Shah
    • , Dana Pueschl
    •  & Katherine L. Nathanson

  • Article
    | Open Access

    Consensus sequence-based methods for self-correction of long-read sequencing data are affected by biases that can mask true variants characterizing little-covered or low-frequency haplotypes. Here, to address this issue, the authors develop a variation graph-based method for performing haplotype-aware self-correction of long reads.

    • Xiao Luo
    • , Xiongbin Kang
    •  & Alexander Schönhuth

  • Article
    | Open Access

    RNA velocity can detect the differentiation directionality by modelling sparse unspliced RNAs, but suffers from high estimation errors. Here, the authors develop a computational method called UniTVelo to reinforce the velocity estimation by introducing a unified time and a top-down model design.

    • Mingze Gao
    • , Chen Qiao
    •  & Yuanhua Huang

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