Featured
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| Open AccessDynamic chromatin architecture of the porcine adipose tissues with weight gain and loss
Here the authors study diet-induced weight gain/loss to identify chromatin architectures in adipose tissue (AT) associated obesity in a pig model. They found parallels and species-specific regulatory elements in humans and pigs that underpin AT specialization.
- Long Jin
- , Danyang Wang
- & Mingzhou Li
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Article
| Open AccessCell-attribute aware community detection improves differential abundance testing from single-cell RNA-Seq data
Single-cell technologies allow quantification of cell-types in human tissues, yet detecting if their abundance changes in aging or disease is challenging. By using cell-attribute aware clustering, this work presents a differential abundance testing algorithm with increased power.
- Alok K. Maity
- & Andrew E. Teschendorff
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Article
| Open AccessM1BP is an essential transcriptional activator of oxidative metabolism during Drosophila development
The transcriptional regulation of mitochondrial oxidative phosphorylation gene expression is poorly understood. Using the developing Drosophila flight muscle, the authors identify the transcription factor M1BP as a new major regulator of this process.
- Gabriela Poliacikova
- , Marine Barthez
- & Andrew J. Saurin
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| Open AccessCell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes
Sex differences in brain transcriptomics have unknown cell type specificity. Here, authors show concordant cortical transcriptomic patterns in depression within individual cell types between sexes, but distinctly affected top cell types and genes.
- Malosree Maitra
- , Haruka Mitsuhashi
- & Corina Nagy
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| Open AccessHigh-throughput and high-accuracy single-cell RNA isoform analysis using PacBio circular consensus sequencing
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
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| Open AccessSingle-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis
Germ cells undergo dramatic chromatin and transcriptomic changes during spermatogenesis, though how this is controlled is not well established. Here they show that RNA-binding protein DDX43 directs the spermatid differentiation trajectory and regulates chromatin remodeling in spermiogenesis, which is partially mediated by its target gene Elfn2.
- Huanhuan Tan
- , Weixu Wang
- & Ke Zheng
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| Open AccessSingle-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers
Mutations in amyloid precursor protein (APP) and presenilin 1 (PSEN1) cause autosomal dominant AD (ADAD). Here, the authors perform single-nucleus RNA-sequencing of ADAD and other disease risk modifying variant carriers and report altered expression states of specific brain cell types.
- Logan Brase
- , Shih-Feng You
- & Oscar Harari
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Article
| Open AccessMulti-omic underpinnings of epigenetic aging and human longevity
Here, the authors integrate genomic, bulk and single-cell transcriptomic, and metabolomic data sets to compare the biological underpinning of four epigenetic clocks and human longevity, offering novel insights into aging biology.
- Lucas A. Mavromatis
- , Daniel B. Rosoff
- & Falk W. Lohoff
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Article
| Open AccessTime-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice
The timing of NAD + supply determines its efficacy to treat metabolic disease. Here, the authors show that increasing NAD + at the early active phase maximizes weight loss and glucose regulation in mice. NAD + can displace the phase of the liver clock which can cause circadian misalignment.
- Quetzalcoatl Escalante-Covarrubias
- , Lucía Mendoza-Viveros
- & Lorena Aguilar-Arnal
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Article
| Open AccessPan-cancer classification of single cells in the tumour microenvironment
The accuracy and granularity of classifying cell types in the tumour microenvironment (TME) from single-cell RNA-seq data is impacted by heterogeneity among cancer cells and similarities among functionally related immune cells. Here, the authors develop scATOMIC, a tumour and TME cell type classifier based on a hierarchical approach that can be applied to pan-cancer datasets.
- Ido Nofech-Mozes
- , David Soave
- & Sagi Abelson
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Article
| Open AccessSpatial transcriptomics using multiplexed deterministic barcoding in tissue
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
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Article
| Open AccessWell-TEMP-seq as a microwell-based strategy for massively parallel profiling of single-cell temporal RNA dynamics
Gene expression of cells is a heterogeneous and dynamic program involved in various biological processes. Here, authors develop Well-TEMPseq, a high-throughput, cost-effective, and accurate method for massively parallel profiling of the temporal dynamics of single-cell gene expression.
- Shichao Lin
- , Kun Yin
- & Chaoyong Yang
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Article
| Open AccessQuantitative analysis of C. elegans transcripts by Nanopore direct-cDNA sequencing reveals terminal hairpins in non trans-spliced mRNAs
C. elegans long read transcriptomic analysis provides evidence that non-trans-spliced mRNAs display a terminal a hairpin structure mimicking the Spliced Leader. This provides an explanation how the main maturation system might be bypassed.
- Florian Bernard
- , Delphine Dargère
- & Denis Dupuy
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Article
| Open AccessRNA splicing analysis using heterogeneous and large RNA-seq datasets
Here the authors develop MAJIQ v2 to address challenges in detection, quantification, and visualization of RNA splicing variations from large heterogeneous RNA-Seq datasets. They then apply it to analyze 2,335 samples from 13 brain subregions.
- Jorge Vaquero-Garcia
- , Joseph K. Aicher
- & Yoseph Barash
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| Open AccessBdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity
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
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| Open AccessReconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis
Delineating the cellular composition of tumour boundaries in spatial transcriptomics (ST) data is challenging. Here, the authors develop Cottrazm to integrate ST with histological imaging and single-cell data, identify the malignant and non-malignant tissue boundaries, deconvolute cell-type composition, and reconstruct cell type-specific gene expression profiles.
- Zhenzhen Xun
- , Xinyu Ding
- & Youqiong Ye
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| Open AccessDifferential regulation of mRNA stability modulates transcriptional memory and facilitates environmental adaptation
Transcriptional memory is key for cellular adaptation. Here the authors show that differences in mRNA stability and mRNA degradation machinery between naïve and primed cells facilitate faster gene expression response to repeated stimuli.
- Bingnan Li
- , Patrice Zeis
- & Vicent Pelechano
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Article
| Open AccessA molecular atlas reveals the tri-sectional spinning mechanism of spider dragline silk
The genetic basis of spider major ampullate (Ma) gland silk production remains unknown. Hu et al. unveil a molecular atlas of this gland for the golden orb-weaving spider combining genome assembly and multiomics, revealing the single-cell spatial architecture of silk production in the Ma gland.
- Wenbo Hu
- , Anqiang Jia
- & Yi Wang
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Article
| Open AccessLipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response
Circulating lipids can influence immune cell function, which could have implications for inflammatory diseases such as rheumatoid arthritis. Here, the authors use Mendelian randomization to identify genes whose expression is influenced by triglyceride levels in blood, implicating genes involved in lipid metabolism and allergic response.
- Koen F. Dekkers
- , Roderick C. Slieker
- & Bastiaan T. Heijmans
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| Open AccessCorrelated evolution of social organization and lifespan in mammals
To elucidate the relationship between sociality and longevity, the authors perform phylogenetic and transcriptomic comparative analysis of mammals. They find that group-living species lived longer than solitary species and identify 31 genes, hormones, and immunity-related pathways involved in this connection.
- Pingfen Zhu
- , Weiqiang Liu
- & Xuming Zhou
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| Open AccessSingle-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer
Fibroblast heterogeneity is a prominent but poorly understood feature of solid tumours. Here three major fibroblast subpopulations in non-small cell lung cancer are identified and characterised through single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry.
- Christopher J. Hanley
- , Sara Waise
- & Gareth J. Thomas
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| Open AccessSpatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples
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
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| Open Accessscm6A-seq reveals single-cell landscapes of the dynamic m6A during oocyte maturation and early embryonic development
Modification of RNA with N6-methyladenosine can regulate RNA metabolism. Here they developed scm6A-seq to profile the methylome and transcriptome in single cells, and reveal the functions of m6A modification during oocyte maturation and early embryo development.
- Huan Yao
- , Chun-Chun Gao
- & Yun-Gui Yang
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Article
| Open AccessMolecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis
Richter syndrome (RS) is the transformation of chronic lymphocytic leukaemia (CLL) into aggressive lymphoma, in most cases diffuse large B-cell lymphoma (DLBCL). Here, the authors characterize the DNA methylation and transcriptomic profiles of RS samples, find a clonally-related CLL epigenetic imprint, and develop classifiers for “RS-type” de novo DLBCLs.
- Julien Broséus
- , Sébastien Hergalant
- & Stephan Stilgenbauer
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| Open AccessSemi-quantitative detection of pseudouridine modifications and type I/II hypermodifications in human mRNAs using direct long-read sequencing
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
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Article
| Open AccessTranscriptional vulnerabilities of striatal neurons in human and rodent models of Huntington’s disease
In human and mouse models of Huntington’s disease, Matsushima, Pineda et al. show, using snRNAsequencing, the two axes defining identities of striatal projection neurons are multiplexed and differentially compromised, calling for distinct therapies.
- Ayano Matsushima
- , Sergio Sebastian Pineda
- & Ann M. Graybiel
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Article
| Open AccessMolecular subtypes of ALS are associated with differences in patient prognosis
Variability in ALS disease onset and progression are poorly understood. Our work identifies three distinct molecular states in post-mortem tissue that capture some of the observed differences in patient age of onset and survival.
- Jarrett Eshima
- , Samantha A. O’Connor
- & Barbara S. Smith
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Article
| Open AccessA comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer
T cell exhaustion in breast tumours remains to be fully characterised. Here, single cell transcriptomics and imaging mass cytometry analysis of luminal breast tumours with or without exhausted T cells suggests distinct patterns of PD-1 and CXCL13 expression in T cells, and of MHC-I, but not PD-L1, expression in tumour cells.
- Sandra Tietscher
- , Johanna Wagner
- & Bernd Bodenmiller
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| Open AccessSingle-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons
How molecular diversity in neurons links to versatile functions is elusive. Here the authors profiled embryonic spinal motor neurons with single-cell RNAseq and identified molecular subtypes targeting distinct muscle groups in different species.
- Ee Shan Liau
- , Suoqin Jin
- & Jun-An Chen
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| Open AccessTranscriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Although myeloid cell dysfunction has been observed in COVID-19, the underlying mechanisms remain incompletely understood. Here, the authors demonstrate that monocytes from patients with mild to moderate COVID-19 show a blunted innate immune response and a pro-thrombotic signature following secondary SARS-CoV-2 challenge.
- Allison K. Maher
- , Katie L. Burnham
- & Margarita Dominguez-Villar
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Article
| Open AccessExon junction complex shapes the m6A epitranscriptome
Here the authors show the exon junction complex (EJC) component, EIF4A3, locally restricts METTL3- mediated mRNA methylation at exon junctions to explain the observed widespread enrichment of m6A modification in 3’ untranslated regions.
- Xin Yang
- , Robinson Triboulet
- & Richard I. Gregory
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| Open AccessSingle-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity
Knowledge of the transcriptional programs of human kidney cell populations at homeostasis is limited. Here, the authors show sex-based differences in gene expression of kidney parenchymal cells and examine the complexity of kidney-resident immune cells using single cell RNA sequencing of healthy living kidney donors.
- Caitriona M. McEvoy
- , Julia M. Murphy
- & Sarah Q. Crome
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| Open AccessSpatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding
Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here the authors introduce Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data.
- Rongbo Shen
- , Lin Liu
- & Jianhua Yao
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| Open AccessThe transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are age-related pathologies in which alterations of hematopoietic stem cells lead to abnormal formation of blood cells. Here, the authors study the lesions that these cells undergo in aging and disease, characterizing a factor whose alteration in MDS leads to abnormal blood cell production.
- Nerea Berastegui
- , Marina Ainciburu
- & Felipe Prosper
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| Open AccessA unified computational framework for single-cell data integration with optimal transport
Integrating heterogeneous single-cell multi-omics as well as spatially resolved transcriptomic data remains a major challenge. Here the authors report a unified single-cell data integration framework using an unbalanced optimal transport-based deep network.
- Kai Cao
- , Qiyu Gong
- & Lin Wan
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| Open AccessAltered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila
La proteins are conserved factors critical for the maturation of RNA polymerase III transcripts. In the ciliate T. thermophila and related alveolates, La proteins have a novel domain arrangement and are linked to a distinct pre-tRNA processing pathway.
- Kyra Kerkhofs
- , Jyoti Garg
- & Mark A. Bayfield
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Article
| Open AccessSOTIP is a versatile method for microenvironment modeling with spatial omics data
Methods that analyse heterogeneity and compare tissue microenvironments using spatial omics data are challenging to develop. Here, the authors present SOTIP, a method that can perform spatial heterogeneity, spatial domain, and differential microenvironment analyses across multiple spatial omics modalities.
- Zhiyuan Yuan
- , Yisi Li
- & Michael Q. Zhang
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Article
| Open AccessA single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma
Studying the cell composition of acral melanoma at the single-cell level could provide some clues about its poor response to immunotherapy. Here, the authors analyse acral and cutaneous melanoma patient samples using single-cell RNA-sequencing, and reveal a severe immunosuppressive state in acral melanomas
- Chao Zhang
- , Hongru Shen
- & Jilong Yang
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Article
| Open AccessPostnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34+ stromal cell subsets
Lymph nodes in various locations of the body differ in their cell composition and gene expression signatures. Here authors show that the rapid postnatal expansion of lymph nodes is governed by CD34 + stromal cells and fibroblastic reticular stromal cell progenitors, distinguished by intrinsic, microbiome-independent core epigenetic blueprints.
- Joern Pezoldt
- , Carolin Wiechers
- & Jochen Huehn
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Article
| Open AccessSpatially aware dimension reduction for spatial transcriptomics
Spatial transcriptomics analyses can be affected by noise and spatial correlation across tissue locations. Here, the authors develop SpatialPCA, a spatially-aware dimensionality reduction method that explicitly models spatial correlation structures, and show its application to the analysis of healthy and tumour tissues.
- Lulu Shang
- & Xiang Zhou
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Article
| Open AccessGenomic signatures of recent convergent transitions to social life in spiders
Sociality has evolved repeatedly in arthropods. Tong et al. compare the genomes of 22 spider species with a range of social complexity and eight independent origins of sociality, and identify specific genetic changes associated with the evolution of sociality in spiders.
- Chao Tong
- , Leticia Avilés
- & Timothy A. Linksvayer
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Article
| Open AccessA non-coding GWAS variant impacts anthracycline-induced cardiotoxic phenotypes in human iPSC-derived cardiomyocytes
Germline variants may pre-dispose patients to an increased risk of developing anthracycline-induced cardiotoxicity. This report provides insights into the mechanism by which a common genetic variant, rs28714259, may confer an increased risk of cardiac damage.
- Xi Wu
- , Fei Shen
- & Bryan Paul Schneider
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Article
| Open AccessCLIMB: High-dimensional association detection in large scale genomic data
Comparisons among experimental results with large amounts of data can be more precise and meaningful when done across multiple different conditions simultaneously. Koch et al. introduce a method, called CLIMB, that does this, and captures interpretable and biologically meaningful information.
- Hillary Koch
- , Cheryl A. Keller
- & Qunhua Li
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Article
| Open AccessA flexible cross-platform single-cell data processing pipeline
As the throughput of single-cell RNA-seq studies increases, there is a need for tools that can make the data analysis steps more streamlined and convenient. Here, the authors develop UniverSC, a tool that unifies single-cell RNA-seq analysis workflows and also facilitates their use for non-experts.
- Kai Battenberg
- , S. Thomas Kelly
- & Aki Minoda
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Article
| Open AccessSystematic characterization of cancer transcriptome at transcript resolution
Modification of transcribed mRNAs enables regulation of transcription but its extent in cancer cells is incompletely understood. Here, the authors analyse transcript assembly in over 1000 cancer cell lines and find unannotated transcripts are common, and are associated with drug sensitivity.
- Wei Hu
- , Yangjun Wu
- & Shengli Li
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Article
| Open AccessspeedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing
Chimeric antigen receptors (CAR) are a promising option for cell-based immunotherapy for cancer and other immune diseases. Here the authors develop speedingCARs, an integrated CAR design and screening platform based on modular signaling domain shuffling and single cell transcriptomic analyses, and test its potential for identifying and validating novel CAR designs.
- Rocío Castellanos-Rueda
- , Raphaël B. Di Roberto
- & Sai T. Reddy
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Article
| Open AccessTranslation and natural selection of micropeptides from long non-canonical RNAs
Translation of 100 to 300 micropeptides from small ORFs within lncRNA was detected by Ribosomal Profiling in Drosophila embryos. These translated small ORFs showed natural selection conserving micropeptide sequence and function.
- Pedro Patraquim
- , Emile G. Magny
- & Juan Pablo Couso
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| Open AccessDe novo analysis of bulk RNA-seq data at spatially resolved single-cell resolution
Current methods to reanalyze bulk RNA-seq at spatially resolved single-cell resolution have limitations. Here, the authors develop Bulk2Space, a spatial deconvolution algorithm using single-cell and spatial transcriptomics as references, providing new insights into spatial heterogeneity within bulk tissue.
- Jie Liao
- , Jingyang Qian
- & Xiaohui Fan
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| Open AccessSUMMIT: An integrative approach for better transcriptomic data imputation improves causal gene identification
Genes with moderate-low expression heritability cannot be sufficiently captured with conventional TWAS. This study introduces a new method, Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction of TWAS by using eQTL summary-level data.
- Zichen Zhang
- , Ye Eun Bae
- & Chong Wu