Focus 26 January 2021

Biotechnology and methods

Methodology development promotes science advancement. Application of new scientific discoveries to biological processes, organisms, or systems can help to sustainably produce products for healing, feeding, or fueling. This page showcases our recent publications that report methodological or biotechnological advances relevant to biological, biomedical, and agricultural sciences.

Featured articles

Context-aware deep learning enables high-efficacy localization of high concentration microbubbles for super-resolution ultrasound localization microscopy

Ultrasound localisation microscopy enables deep tissue microvascular imaging. Here, authors introduce LOCA-ULM, a deep learning pipeline enhancing localisation accuracy in high microbubble concentrations. LOCA-ULM reveals dense cerebrovascular networks and enhances the sensitivity of functional ULM.
- YiRang Shin
- Matthew R. Lowerison
- Pengfei Song
ArticleOpen Access4 Apr 2024 Nature Communications
A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations

While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an E. coli strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.
- Hang Zhou
- Yiwen Zhang
- Baixue Lin
ArticleOpen Access15 Mar 2024 Nature Communications
Engineering intelligent chassis cells via recombinase-based MEMORY circuits

The unification of decision-making, communication, and memory would enable the programming of intelligent biotic systems. Here, the authors achieve this goal by engineering E. coli chassis cells with an array of inducible recombinases that mediate diverse genetic programs.
- Brian D. Huang
- Dowan Kim
- Corey J. Wilson
ArticleOpen Access18 Mar 2024 Nature Communications
Microinterfaces in biopolymer-based bicontinuous hydrogels guide rapid 3D cell migration

Extracellular microinterfaces provide cells with migration tracks in vivo. Here, the authors introduce these microtracks into bicontinuous hydrogels to elicit rapid cell migration in 3-dimensional contexts.
- Karen L. Xu
- Nikolas Di Caprio
- Jason A. Burdick
ArticleOpen Access29 Mar 2024 Nature Communications
Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance

RNA splicing serves as a critical layer of gene expression regulation. Here, authors introduce SCASL for investigating the heterogeneity of RNA splicing landscapes at single-cell resolution, offering a novel scheme for classifying cell identities with physiological relevance.
- Xianke Xiang
- Yao He
- Xuerui Yang
ArticleOpen Access9 Mar 2024 Nature Communications
Statistical method scDEED for detecting dubious 2D single-cell embeddings and optimizing t-SNE and UMAP hyperparameters

2D visualisation of single-cell data is highly impacted by the hyperparameter setting of the 2D embedding method, such as t-SNE and UMAP. Here, authors develop a statistical method scDEED to detect dubious cell embeddings and optimise the hyperparameter setting for trustworthy visualisation.
- Lucy Xia
- Christy Lee
- Jingyi Jessica Li
ArticleOpen Access26 Feb 2024 Nature Communications
Fudging the volcano-plot without dredging the data

Selecting omic biomarkers using both their effect size and their differential status significance (i.e., selecting the “volcano-plot outer spray”) has long been equally biologically relevant and statistically troublesome. However, recent proposals are paving the way to resolving this dilemma.
- Thomas Burger
CommentOpen Access15 Feb 2024 Nature Communications
Edible mycelium bioengineered for enhanced nutritional value and sensory appeal using a modular synthetic biology toolkit

Fungi have the potential to produce sustainable foods for a growing population, but current products are based on a small number of strains with inherent limitations. Here, the authors develop genetic tools for an edible fungus and engineer its nutritional value and sensory appeal for alternative meat applications.
- Vayu Maini Rekdal
- Casper R. B. van der Luijt
- Jay D. Keasling
ArticleOpen Access14 Mar 2024 Nature Communications
Advancing the scale of synthetic biology via cross-species transfer of cellular functions enabled by iModulon engraftment

Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes. Here the authors present iModulon-based engineering for precise identification of genes for cross-species function transfer to streamline synthetic biology for strain development and biomanufacturing.
- Donghui Choe
- Connor A. Olson
- Bernhard O. Palsson
ArticleOpen Access15 Mar 2024 Nature Communications
OrthoID: profiling dynamic proteomes through time and space using mutually orthogonal chemical tools

Proteomics at the organelle contact site remains challenging due to the spatial and temporal dynamics of proteins. Here, the authors developed OrthoID, a mutually orthogonal dual enzymatic proteomics approach to explore the proteome at the contact site of the endoplasmic reticulum and mitochondria.
- Ara Lee
- Gihyun Sung
- Kimoon Kim
ArticleOpen Access29 Feb 2024 Nature Communications
MAIVeSS: streamlined selection of antigenically matched, high-yield viruses for seasonal influenza vaccine production

Vaccines combat global influenza threats, relying on timely selection of optimal seed viruses. Here, authors introduce MAIVeSS, a machine learning assisted framework to streamline vaccine seed virus selection using genomic sequence, expediting seasonal flu vaccine production and supply.
- Cheng Gao
- Feng Wen
- Xiu-Feng Wan
ArticleOpen Access6 Feb 2024 Nature Communications
Semi-supervised integration of single-cell transcriptomics data

Batch effects hinder multi-sample single-cell data analyses. Here, authors present STACAS, a scalable single-cell RNA-seq data integration tool that uses prior cell type knowledge to preserve biological variability, demonstrating robustness to noisy input cell type labels.
- Massimo Andreatta
- Léonard Hérault
- Santiago J. Carmona
ArticleOpen Access29 Jan 2024 Nature Communications
SiFT: uncovering hidden biological processes by probabilistic filtering of single-cell data

Cells simultaneously encode multiple signals, some harder to recover. Here, authors introduce SiFT (Signal FilTering), a kernel-based projection method, revealing underlying biological processes in single-cell data.
- Zoe Piran
- Mor Nitzan
ArticleOpen Access26 Jan 2024 Nature Communications
Anti-correlated feature selection prevents false discovery of subpopulations in scRNAseq

Typical single-cell RNAseq pipelines will subcluster homogeneous cells. Here, authors present a computational algorithm for accurately identifying cell-type marker genes in single-cell data analysis with a low false discovery rate.
- Scott R. Tyler
- Daniel Lozano-Ojalvo
- Eric E. Schadt
ArticleOpen Access24 Jan 2024 Nature Communications
Rational strain design with minimal phenotype perturbation

No consensus exists on the computationally tractable use of dynamic models for strain design. To tackle this, the authors report a framework, nonlinear-dynamic-model-assisted rational metabolic engineering design, for efficiently designing robust, artificially engineered cellular organisms.
- Bharath Narayanan
- Daniel Weilandt
- Vassily Hatzimanikatis
ArticleOpen Access24 Jan 2024 Nature Communications
Compositional and temporal division of labor modulates mixed sugar fermentation by an engineered yeast consortium

Synthetic microbial communities are suitable for mixed substrates fermentation and long metabolic pathway engineering. Here, the authors combine fermentation experiments with mathematical modeling to reveal the effect of compositional and temporal changes on division of labor in cellulosic ethanol production using two yeast strains.
- Jonghyeok Shin
- Siqi Liao
- Yong-Su Jin
ArticleOpen Access26 Jan 2024 Nature Communications
A genetic circuit on a single DNA molecule as an autonomous dissipative nanodevice

Achieving genetic circuits on single DNA molecules could have varied applications. Here, authors observed proteins emerging from single DNA molecules through coupled transcription-translation complexes, and show that nascent proteins lingered on DNA, regulating cascaded reactions on the same DNA and allowing the design of a pulsatile genetic circuit.
- Ferdinand Greiss
- Nicolas Lardon
- Roy Bar-Ziv
ArticleOpen Access29 Jan 2024 Nature Communications
Enhancing geometric representations for molecules with equivariant vector-scalar interactive message passing

Utilising geometric information and reducing computational costs are key challenges in the molecular modelling field. Here, authors propose ViSNet, which efficiently extracts geometric features, accurately predicts molecular properties, and drives simulations with interpretability.
- Yusong Wang
- Tong Wang
- Tie-Yan Liu
ArticleOpen Access5 Jan 2024 Nature Communications
BIDCell: Biologically-informed self-supervised learning for segmentation of subcellular spatial transcriptomics data

Subcellular in situ spatial transcriptomics offers the promise to address biological problems that were previously inaccessible but requires accurate cell segmentation to uncover insights. Here, authors present BIDCell, a biologically informed, deep learning-based cell segmentation framework.
- Xiaohang Fu
- Yingxin Lin
- Jean Y. H. Yang
ArticleOpen Access13 Jan 2024 Nature Communications
MarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer

Identifying rare cell populations is key to understanding cancer progression and response to therapy. Here, authors introduce MarsGT, an end-to-end deep learning model for rare cell population identification from scMulti-omics data.
- Xiaoying Wang
- Maoteng Duan
- Qin Ma
ArticleOpen Access6 Jan 2024 Nature Communications
Derivation of human primordial germ cell-like cells in an embryonic-like culture

Derivation of human primordial germ cell-like cells (hPGCLCs) is critical for reproductive medicine. Here, authors report the induction of hPGCLCs in a bioengineered human pluripotent stem cell culture that mimics peri-implantation human development.
- Sajedeh Nasr Esfahani
- Yi Zheng
- Jianping Fu
ArticleOpen Access2 Jan 2024 Nature Communications
Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer

Somatic cloning of rhesus monkey has not been successful until now. Here, authors report epigenetic abnormalities in SCNT embryos and placentas and develop a trophoblast replacement method that enables them to successful clone of a healthy male rhesus monkey.
- Zhaodi Liao
- Jixiang Zhang
- Qiang Sun
ArticleOpen Access16 Jan 2024 Nature Communications
rworkflows: automating reproducible practices for the R community

Reproducibility is essential for the progress of research, yet achieving it remains elusive even in computational fields. Here, authors develop the rworkflows suite, making robust CI/CD workflows easy and freely accessible to all R package developers.
- Brian M. Schilder
- Alan E. Murphy
- Nathan G. Skene
ArticleOpen Access2 Jan 2024 Nature Communications
ECOLE: Learning to call copy number variants on whole exome sequencing data

Copy number variants (CNV) are shown to contribute to the etiology of various genetic disorders. Here, authors present ECOLE, a deep learning-based somatic and germline CNV caller for WES data. Utilising a variant of the transformer architecture, the model is trained to call CNVs per exon.
- Berk Mandiracioglu
- Furkan Ozden
- A. Ercument Cicek
ArticleOpen Access2 Jan 2024 Nature Communications
JOINTLY: interpretable joint clustering of single-cell transcriptomes

Batch integration is a critical yet challenging step in many single-cell RNA-seq analysis workflows. Here, authors present JOINTLY, a hybrid linear and non-linear NMF-based algorithm, providing interpretable and robust cell clustering against over-integration.
- Andreas Fønss Møller
- Jesper Grud Skat Madsen
ArticleOpen Access20 Dec 2023 Nature Communications
Deciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON

Deciphering the roles of gene regulation in cell fate decisions is crucial. Here, authors present CEFCON, a network-based framework that reveals cell-lineage-specific gene regulatory networks and identifies driver regulators controlling cell fate decisions from single-cell transcriptomics data.
- Peizhuo Wang
- Xiao Wen
- Jianyang Zeng
ArticleOpen Access20 Dec 2023 Nature Communications
STalign: Alignment of spatial transcriptomics data using diffeomorphic metric mapping

Spatial transcriptomics (ST) enables gene expression characterisation within tissue sections, but comparing across sections and technologies remains challenging. Here, authors develop STalign to spatially align ST data and demonstrate applications including aligning to common coordinate frameworks.
- Kalen Clifton
- Manjari Anant
- Jean Fan
ArticleOpen Access8 Dec 2023 Nature Communications
Generation of three-dimensional meat-like tissue from stable pig epiblast stem cells

Cultured meat technology promises to alleviate protein shortages, but still faces many challenges. Here, the authors achieve serum-free myogenic differentiation of porcine pre-gastrulation epiblast stem cells and generate meat-like tissue via edible plant-based scaffolds without any animal compounds.
- Gaoxiang Zhu
- Dengfeng Gao
- Jianyong Han
ArticleOpen Access9 Dec 2023 Nature Communications
Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts

The functional heterogeneity of autophagy in endothelial cells during angiogenesis remains incompletely understood. Here, the authors apply a 3D angiogenesis-on-a-chip coupled with single-cell RNA sequencing to find distinct autophagy functions in two different endothelial cell populations during angiogenic sprouting.
- Somin Lee
- Hyunkyung Kim
- Noo Li Jeon
ArticleOpen Access3 Jan 2024 Nature Communications
Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity

PSC-brain organoids are typically formed by static medium switches. Here, authors show that a temporal morphogen gradient during neural induction allows the formation of well-specified cortical organoids with a self-organized single neuroepithelium.
- Anna Pagliaro
- Roxy Finger
- Benedetta Artegiani
ArticleOpen Access28 Nov 2023 Nature Communications
Efficient generation of a self-organizing neuromuscular junction model from human pluripotent stem cells

Here, Urzi et al. pioneered a 2D self-organizing neuromuscular junction (soNMJ) model from human pluripotent stem cells, with implications for neuromuscular disease modeling and drug screening approaches.
- Alessia Urzi
- Ines Lahmann
- Mina Gouti
ArticleOpen Access19 Dec 2023 Nature Communications
CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves

Dose-response curves are ubiquitous in pharmacology and biology, yet potency and effect size are often estimated even when there is no response. Here, authors present a statistical framework to assess curve significance and demonstrate how this aids drug mode of action analysis in large public datasets.
- Florian P. Bayer
- Manuel Gander
- Matthew The
ArticleOpen Access30 Nov 2023 Nature Communications
Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.
- A. Brenda Kapingidza
- Daniel J. Marston
- Mihai L. Azoitei
ArticleOpen Access30 Nov 2023 Nature Communications
An on-demand bioresorbable neurostimulator

Despite promising advantages, bioresorbable electronics face practical limitations due to unpredictable device lifetimes. Here, the authors introduce an on-demand bioresorbable neurostimulator powered by biosafe ultrasound to treat peripheral nerve injury and neuropathies.
- Dong-Min Lee
- Minki Kang
- Sang-Woo Kim
ArticleOpen Access11 Nov 2023 Nature Communications
3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry

Geometrical complexities of blood vessels alter biophysical behaviors of circulating tumor cells, influencing cancer metastasis. Here, the authors develop a 3D bioprinted in vitro brain blood vessel-on-a-chip to investigate continuities between vascular geometry and metastatic cancer development.
- Wonbin Park
- Jae-Seong Lee
- Dong-Woo Cho
ArticleOpen Access24 Nov 2023 Nature Communications
The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO₂ in the yeast Komagataella phaffii

One carbon compounds such as CO₂, methanol and formate are cost-effective and environmentally friendly microbial feedstocks for biomanufacturing. Here, the authors report the oxygen tolerant reductive glycine pathway in Komagataella phaffii can co-assimilate CO₂, methanol and formate.
- Bernd M. Mitic
- Christina Troyer
- Diethard Mattanovich
ArticleOpen Access27 Nov 2023 Nature Communications
Discovery and remodeling of Vibrio natriegens as a microbial platform for efficient formic acid biorefinery

Formic acid (FA) is a promising CO2-equivalent feedstock for onecarbon biorefinery, but microbial host that can efficiently utilize FA is unavailable. Here, the authors engineer a non-native closed loop in Vibrio natriegens and demonstrate its application in promoting FA utilization.
- Jinzhong Tian
- Wangshuying Deng
- Yang Gu
ArticleOpen Access27 Nov 2023 Nature Communications
Wireless, battery-free, multifunctional integrated bioelectronics for respiratory pathogens monitoring and severity evaluation

The SARS-CoV-2 pandemic highlighted our need for methods that allow rapid viral surveillance. Here, authors report a wireless, battery-free and wearable self-diagnosis platform that can continuously capture viral particles, diagnose infection status and evaluate symptom severity via breath and blow.
- Hu Li
- Huarui Gong
- Xinge Yu
ArticleOpen Access20 Nov 2023 Nature Communications
A knowledge-guided pre-training framework for improving molecular representation learning

Accurate property prediction relies on effective molecular representation. Here, the authors introduce KPGT, a knowledge-guided self-supervised framework that improves molecular representation, leading to superior predictions of molecular properties and advancing AI-driven drug discovery.
- Han Li
- Ruotian Zhang
- Jianyang Zeng
ArticleOpen Access21 Nov 2023 Nature Communications
Dimension-agnostic and granularity-based spatially variable gene identification using BSP

Identifying spatially variable genes (SVGs) is essential for linking molecular cell functions with tissue phenotypes. Here, authors introduce a non-parametric model that detects SVGs from two or three-dimensional spatial transcriptomics data by comparing gene expression patterns at granularities.
- Juexin Wang
- Jinpu Li
- Dong Xu
ArticleOpen Access14 Nov 2023 Nature Communications
Spatial-linked alignment tool (SLAT) for aligning heterogenous slices

Spatial omics technologies reveal the organisation of cells in various biological systems. Here, authors propose SLAT, a graph-based algorithm for aligning heterogenous data across technologies, modalities and timepoints, enabling spatiotemporal reconstruction of complex developmental processes.
- Chen-Rui Xia
- Zhi-Jie Cao
- Ge Gao
ArticleOpen Access9 Nov 2023 Nature Communications
Nanomechanical action opens endo-lysosomal compartments

Endo-lysosomal escape is a highly inefficient process. Here the authors present a lipid-based nanoscale molecular machine that achieves efficient cytosolic transport of biologics by destabilizing endo-lysosomal compartments through nanomechanical action upon light irradiation.
- Yu Zhao
- Zhongfeng Ye
- Qiaobing Xu
ArticleOpen Access20 Oct 2023 Nature Communications
CamoTSS: analysis of alternative transcription start sites for cellular phenotypes and regulatory patterns from 5' scRNA-seq data

Five-prime single-cell RNA-seq, especially the read 1, has precise capture of transcription start sites (TSS), but such information is often overlooked. Here, authors present a computational method suite, CamoTSS, to precisely identify TSS and quantify its expression, enabling effective detection of alternative TSS usage in different biological processes.
- Ruiyan Hou
- Chung-Chau Hon
- Yuanhua Huang
ArticleOpen Access9 Nov 2023 Nature Communications
NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing

Unlocking the blood proteome requires exquisite sensitivity and multiplexing to detect low and high abundance proteins simultaneously. Here the authors describe a 200-plex immunoassay with attomolar sensitivity to detect important low abundance proteins in inflammatory diseases and COVID-19.
- Wei Feng
- Joanne C. Beer
- Xiao-Jun Ma
ArticleOpen Access9 Nov 2023 Nature Communications
NeST: nested hierarchical structure identification in spatial transcriptomic data

A wide variety of tissues exhibit nested hierarchical organisation of cells in gene expression and activities. Here, authors present NeST, a method for spatial transcriptomics to identify such structures and uncover their functions via ligand-receptor communication, in both two and three dimensions.
- Benjamin L. Walker
- Qing Nie
ArticleOpen Access17 Oct 2023 Nature Communications
RNA-based translation activators for targeted gene upregulation

Many diseases are driven by the insufficient expression of critical genes, but few technologies are capable of rescuing these endogenous protein levels. Here, Cao et al. present an RNA-based technology that boosts protein production from endogenous mRNAs by upregulating their translation.
- Yang Cao
- Huachun Liu
- Bryan C. Dickinson
ArticleOpen Access26 Oct 2023 Nature Communications
Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging

l-Lactate is increasingly recognized as a key metabolite and signalling molecule in mammals, but the methods to investigate it in vivo have been limited. Here, authors report a pair of improved biosensors—one green and one red—for visualizing l-lactate both inside and outside of cells.
- Yusuke Nasu
- Abhi Aggarwal
- Robert E. Campbell
ArticleOpen Access27 Oct 2023 Nature Communications
Deep flanking sequence engineering for efficient promoter design using DeepSEED

Designing promoters with desired properties is crucial in synthetic biology. Here, authors introduce DeepSEED, an AI-aided flanking sequence optimisation framework which combines expert knowledge with deep learning techniques to efficiently design promoters in both eukaryotic and prokaryotic cells.
- Pengcheng Zhang
- Haochen Wang
- Xiaowo Wang
ArticleOpen Access9 Oct 2023 Nature Communications

Biotechnology and methods

Featured articles

Search

Quick links