Featured
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| Open AccessAn oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli
Echinocandins are antifungal drugs that inhibit hyphal growth and induce lysis of hyphal tip compartments in pathogenic Aspergillus species. Here, Calise et al. show that echinocandins induce production of a fungal oxylipin signal, thus triggering hyphal growth changes that reduce hyphal tip lysis and confer echinocandin tolerance.
- Dante G. Calise
- , Sung Chul Park
- & Nancy P. Keller
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Article
| Open AccessMutation characteristics and molecular evolution of ovarian metastasis from gastric cancer and potential biomarkers for paclitaxel treatment
‘Gastric cancer metastasis to the ovary is difficult to treat and is not fully understood. Here, the authors characterized mutations in a cohort of matched primary and metastatic disease, and found mutations, including in CLDN18, could predict treatment response to paclitaxel.
- Pengfei Yu
- , Can Hu
- & Xiangdong Cheng
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Article
| Open AccessTargeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow
Excessive bone marrow adipocytes accumulation is involved in bone deterioration. Here, the authors show that adipocyte ESRRA abrogation promotes osteogenesis and vascular formation in adipocyte-rich bone marrow via oppositely regulating the expression and secretion of leptin and SPP1.
- Tongling Huang
- , Zhaocheng Lu
- & Min Guan
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Article
| Open AccessGiant organelle vesicles to uncover intracellular membrane mechanics and plasticity
The biophysical properties of cellular organelles are difficult to study directly. Here, the authors generate and characterize osmotically-expanded giant vesicles of several organelles, which maintain some of their functional properties.
- Alexandre Santinho
- , Maxime Carpentier
- & Abdou Rachid Thiam
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Article
| Open AccessArabidopsis SBT5.2 and SBT1.7 subtilases mediate C-terminal cleavage of flg22 epitope from bacterial flagellin
Plants initiate specific defense responses by recognizing flg22 peptide epitope derived from flagellin, the major structural protein of the bacterial flagellum. Here, the authors identified two plant subtilases, SBT5.2 and SBT1.7, as specific proteases responsible for cleaving the peptide epitope.
- Sayaka Matsui
- , Saki Noda
- & Yoshikatsu Matsubayashi
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Article
| Open AccessIL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube
In pelvic inflammatory disease, host immune responses to Neisseria gonorrhoeae damage Fallopian tube tissue and cause infertility. Here, Garcia et al. show that the cytokine IL-17C induces inflammatory responses, and peptidoglycan fragments reduce transcripts related to tissue integrity.
- Erin M. Garcia
- , Jonathan D. Lenz
- & Joseph P. Dillard
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Article
| Open AccessDiet-omics in the
S tudy ofU rban andR uralC rohn diseaseE volution (SOURCE) cohortExposures rather than genetics likely contribute to the worldwide increased prevalence of Crohn Disease (CD). Here, the authors constructed the Study Of Urban and Rural Crohn disease Evolution (SOURCE), a multicenter and multi-omics cross-sectional study, to identify that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirrored those seen in CD. Reviewer recognition:
- Tzipi Braun
- , Rui Feng
- & Yael Haberman
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Article
| Open AccessOzone as an environmental driver of influenza
Temperature and absolute humidity are associated with influenza activity, and recent data from Hong Kong have suggested ozone as an additional environmental driver. Here, the authors investigate the relationship between ozone and influenza transmission using surveillance data from the USA and find evidence for an inhibitory effect.
- Fang Guo
- , Pei Zhang
- & Linwei Tian
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Article
| Open AccessGenetic association of inflammatory marker GlycA with lung function and respiratory diseases
Here, the authors observed significant genetic correlation of GlycA with lung function, asthma and COPD and identified ten shared loci revealing potential shared biological mechanisms involving ubiquitination and Wnt/β-catenin signaling.
- Yanjun Guo
- , Quanhong Liu
- & Weihong Chen
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Article
| Open AccessA multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma
Correct diagnosis of primary central nervous system lymphoma is key in determining treatment, however, this depends on pathology analysis. Here, the authors develop a deep learning method to diagnose primary nervous system lymphoma from stained whole-slide images.
- Xinke Zhang
- , Zihan Zhao
- & Muyan Cai
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Article
| Open AccessA statistical resolution measure of fluorescence microscopy with finite photons
Abbe’s diffraction limit has been a defining concept for microscopy. With finite photon, photon noise remains one essential factor yet to be considered in the theoretical resolution limit. Here, the authors introduced information-based resolution limit allowing for photon-considered resolution assessment of various microscopy and super-resolution modalities.
- Yilun Li
- & Fang Huang
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Article
| Open AccessA human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations
Copy number alterations in stem cells impair neural crest differentiation and set the stage for neuroblastoma-like traits and tumours. This study hints at early tumourigenesis mechanisms and finds developmental gene signatures linked to prognosis.
- Ingrid M. Saldana-Guerrero
- , Luis F. Montano-Gutierrez
- & Florian Halbritter
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Article
| Open AccessAdjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus
Here, Dillard and Taft-Benz et al. show in a female mouse model how different adjuvants affect inactivated vaccine-mediated protection against homologous SARS-CoV-2 and heterologous SARS-CoV-1-like coronaviruses. They find that an aluminum hydroxide-adjuvanted vaccine can increase risk of adverse outcomes during heterologous infection.
- Jacob A. Dillard
- , Sharon A. Taft-Benz
- & Mark T. Heise
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Article
| Open AccessDiscovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression
CAR T cell immunotherapy for paediatric solid and brain tumours is constrained by the availability of targetable antigens. Here, the authors investigate the landscape of cancer-specific exons as potential targets by analysing 1,532 RNAseq datasets from 16 types of paediatric solid and brain tumours.
- Timothy I. Shaw
- , Jessica Wagner
- & Stephen Gottschalk
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Article
| Open AccessPrimordial germ cell DNA demethylation and development require DNA translesion synthesis
Here the authors show that DNA translesion synthesis affects primordial germ cell DNA demethylation and plays a role in the development of embryonic germ cells.
- Pranay Shah
- , Ross Hill
- & Gerry P. Crossan
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Article
| Open AccessCD74 supports accumulation and function of regulatory T cells in tumors
CD74, the MHC class II invariant chain, was thought to be mainly expressed by antigen presenting cells. Here the authors report that CD74 is overexpressed by human tumor infiltrating regulatory T cells (Tregs) and that its loss affects Treg accumulation and function in tumors.
- Elisa Bonnin
- , Maria Rodrigo Riestra
- & Eliane Piaggio
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Article
| Open AccessSynthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers
EBV (Epstein-Barr virus)-targeted therapy is limited by efficient agents inducing lytic cycle in cancer cells. Here they report a transcriptional activator incorporated into lipid nanoparticles that could specifically activate endogenous BZLF1 and induce lytic reactivation in EBV-positive cancer cells thereby suppress tumor progression.
- Man Wu
- , Pok Man Hau
- & Kwok-Wai Lo
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Article
| Open AccessAcinar to β-like cell conversion through inhibition of focal adhesion kinase
A cure for diabetes could entail an effective cell replacement therapy through generation of new insulinproducing cells. In this study, we show that inhibition of focal adhesion kinase activity results in transdifferentiation of a subset of peri-islet acinar cells into functional insulin producing β-like cells.
- Shakti Dahiya
- , Mohamed Saleh
- & Farzad Esni
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Article
| Open AccessThe DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum
Min and colleagues study post-transcriptional regulation in the malaria parasite. They describe opposing actions of the DDX6-family RNA helicase complex on the decay and protection of specific mRNA targets during development and stress conditions.
- Hui Min
- , Xiaoying Liang
- & Liwang Cui
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Article
| Open AccessAnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics
Annotation of cell types and quantification of their relative localization in tissues remain challenging. Here, the authors present AnnoSpat (Annotator and Spatial Pattern Finder), a computational tool that can automatically identify cell types and quantify cell-cell proximity relationships.
- Aanchal Mongia
- , Fatema Tuz Zohora
- & Robert B. Faryabi
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Article
| Open AccessA non-image-forming visual circuit mediates the innate fear of heights in male mice
The neural basis underlying fear of heights is not well understood. Here the authors identify, in mice, a subcortical route for innate fear of heights, bypassing the primary visual cortex.
- Wei Shang
- , Shuangyi Xie
- & Xiao-Bing Yuan
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Article
| Open AccessFocal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer
Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.
- Franziska Haderk
- , Yu-Ting Chou
- & Trever G. Bivona
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Article
| Open AccessLncRNA-LncDACH1 mediated phenotypic switching of smooth muscle cells during neointimal hyperplasia in male arteriovenous fistulas
Arteriovenous fistulas are the most common vascular access points for hemodialysis, but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia. Here, the author shows that LncDACH1 regulates NIH through the HSP90/ SRPK1/ AKT signaling axis.
- Zhaozheng Li
- , Yao Zhao
- & Jundong Jiao
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Article
| Open AccessCell-penetrating protein-recognizing polymeric nanoparticles through dynamic covalent chemistry and double imprinting
Molecular recognition of proteins is essential for achieving their biological functions but it is challenging to prepare selective protein-binding materials. Here the authors report a method that combines dynamic covalent chemistry and double molecular imprinting to construct protein-recognizing nanoparticles capable of specific inhibition of protein–protein interactions.
- Avijit Ghosh
- , Mansi Sharma
- & Yan Zhao
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Matters Arising
| Open AccessReassessing data quality underlying the recently updated floristic map of the world
- Hong Qian
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Matters Arising
| Open AccessReply to: Reassessing data quality underlying the recently updated floristic map of the world
- Yunpeng Liu
- , Xiaoting Xu
- & Zhiheng Wang
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Article
| Open AccessSynthetic intrinsically disordered protein fusion tags that enhance protein solubility
Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.
- Nicholas C. Tang
- , Jonathan C. Su
- & Ashutosh Chilkoti
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Article
| Open AccessGlobally occurring pelagiphage infections create ribosome-deprived cells
SAR11 bacteria and their phages are abundant in the oceans. Here the authors quantify the number of phage-infected SAR11 cells using microscopy techniques and discover phage-infected cells without any detectable ribosomes. They hypothesize that ribosomal RNA may be used for the synthesis of phage genomes.
- Jan D. Brüwer
- , Chandni Sidhu
- & Bernhard M. Fuchs
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Article
| Open AccessHPK1 citron homology domain regulates phosphorylation of SLP76 and modulates kinase domain interaction dynamics
In this work, the authors unveil a mechanism where the Citron homology domain regulates HPK1’s kinase domain, shedding light on the relationship between HPK1’s structure and function. This enhances our understanding of HPK1, an intracellular target for cancer immunotherapy and provides a direction for immuno-oncology drug discovery.
- Avantika S. Chitre
- , Ping Wu
- & Weiru Wang
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Article
| Open AccessThe complete assembly of human LAT1-4F2hc complex provides insights into its regulation, function and localisation
The amino acid transporter complex LAT1-4F2hc is considered a major drug target for many cancers. Here, the authors apply native mass spectrometry-based approaches to decode a complete LAT1-4F2hc assembly. To do this, they connect post-translational modification and endogenous phospholipid binding to super-dimerization, function and localisation of LAT1-4F2hc.
- Di Wu
- , Renhong Yan
- & Carol V. Robinson
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Article
| Open AccessEndogenous clock-mediated regulation of intracellular oxygen dynamics is essential for diazotrophic growth of unicellular cyanobacteria
The authors investigate the circadian clock in a unicellular diazotrophic cyanobacterium. They demonstrate the role of the clock in regulating intracellular oxygen dynamics, a necessity to accommodate nitrogen fixation in an oxygen-producing cell.
- Anindita Bandyopadhyay
- , Annesha Sengupta
- & Himadri B. Pakrasi
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Article
| Open AccessDisease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls
Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.
- Stanislav Tsitkov
- , Kelsey Valentine
- & Ernest Fraenkel
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Article
| Open AccessMultiplexed representation of others in the hippocampal CA1 subfield of female mice
How the position of conspecifics is represented in the brain is not fully understood. Here authors show that the position of conspecifics is represented relative to self-position in the hippocampus of female mice, which is modulated by context and identity and improved through learning.
- Xiang Zhang
- , Qichen Cao
- & Chenglin Miao
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Article
| Open AccessRegulatory sequence-based discovery of anti-defense genes in archaeal viruses
Little is known about how archaeal viruses counteract host immunity. Here, the authors leverage a viral gene regulatory feature to predict 354 potential anti-defense genes and experimentally validate a CRISPR-Cas I-A inhibitor and an inhibitor of a toxin-antitoxin system.
- Yuvaraj Bhoobalan-Chitty
- , Shuanshuan Xu
- & Xu Peng
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Article
| Open AccessTiming the evolution of phosphorus-cycling enzymes through geological time using phylogenomics
Phosphorus is an essential nutrient which may have influenced Earth’s early biosphere. This study interrogates genomic records, finding potentially phosphate depleted conditions toward the end of the Archean when enzymes for scavenging reduced phosphorus compounds spread throughout the tree of life.
- Joanne S. Boden
- , Juntao Zhong
- & Eva E. Stüeken
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Article
| Open AccessAnomalous dynamics of a passive droplet in active turbulence
The fluctuating dynamics of a passive object suspended in an active fluid can provide fundamental insight into the fundamental non-equilibrium behavior of the fluid. Singh and Chaudhuri theoretically investigate the dynamics of a passive deformable droplet in active nematic turbulence and show how the motion of the droplet is influenced by the interplay of spatial correlations of the flow and the size of the droplet.
- Chamkor Singh
- & Abhishek Chaudhuri
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Article
| Open AccessMultimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions
Please let us know if there are any inaccuracies: ‘Esophageal squamous cell carcinoma is most commonly detected at a late stage, which limits survival and treatment options. Here, the authors utilise whole genome bisulfite sequencing to create a cfDNA framework to detect cfDNA methylation, copy number variants and fragmentation.
- Jiaqi Liu
- , Lijun Dai
- & Zhihua Liu
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Article
| Open AccessUsing genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes
Here, the authors integrate genomic and transcriptomic data obtained from African-ancestry female participants and identify six genes associated with breast cancer risk which provides biological insights into this common cancer in an underrepresented population.
- Jie Ping
- , Guochong Jia
- & Wei Zheng
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Article
| Open AccessA sparse quantized hopfield network for online-continual memory
Brains and neuromorphic systems learn with local learning rules in online-continual learning scenarios. Designing neural networks that learn effectively under these conditions is challenging. The authors introduce a neural network that implements an effective, principled approach to local, online-continual learning on associative memory tasks.
- Nicholas Alonso
- & Jeffrey L. Krichmar
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Article
| Open AccessInvestigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment
The effect of noncoding genetic variation on acute lymphoblastic leukemia treatment response is not fully understood. Here, the authors functionally evaluated variants associated with pharmacological traits and validate the role of rs1247117 in gene regulation impacting therapeutic response.
- Kashi Raj Bhattarai
- , Robert J. Mobley
- & Daniel Savic
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Article
| Open AccessEye movements track prioritized auditory features in selective attention to natural speech
Anatomical overlap of respective brain regions suggests a joint network for attention and eye movements. Here, the authors show that gaze aligns with the acoustics of attended natural speech and differentiates between a target and a distractor in a cocktail party scenario.
- Quirin Gehmacher
- , Juliane Schubert
- & Nathan Weisz
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Article
| Open AccessThe impact of exercise on gene regulation in association with complex trait genetics
It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.
- Nikolai G. Vetr
- , Nicole R. Gay
- & Stephen B. Montgomery
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Article
| Open AccessLarge-language models facilitate discovery of the molecular signatures regulating sleep and activity
The knowledge in the large language model (LLM), generative pre-trained transformer (GPT) 3.5, is elicited to facilitate the discovery of MRE11 in regulating sleep in the presence of conspecifics by a multi-object video tracking system.
- Di Peng
- , Liubin Zheng
- & Luoying Zhang
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Article
| Open AccessStructural mechanism of voltage-gated sodium channel slow inactivation
Inactivation is an intrinsic property of NaV channel, but the mechanism for slow inactivation is not fully understood. Here, authors show a NaVEh structure in a potential slow-inactivated state, elucidating structural basis for slow inactivation.
- Huiwen Chen
- , Zhanyi Xia
- & Daohua Jiang
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Article
| Open AccessCerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases
CSF biomarker concentrations may be influenced by non-disease related interindividual variability. Here, the authors show that reference proteins can capture this variability and enhance the accuracy of Alzheimer’s disease biomarkers.
- Linda Karlsson
- , Jacob Vogel
- & Oskar Hansson
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Article
| Open AccessDevelopment of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy
The development of metal-nucleic acid nanocomposites for therapeutic is limited by poor stability and synthesis efficiency. Here, the authors develop a multi-fragmented aptamer DNAzyme metal-nucleic acid frameworks (MNFs) under milder conditions and demonstrate its preclinical efficacy in gastric cancer.
- Jiaqi Yan
- , Rajendra Bhadane
- & Hongbo Zhang
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Article
| Open AccessGlis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Cyst growth in autosomal dominant polycystic kidney disease (ADPKD) is driven by unknown molecular signals that require the presence of intact primary cilia in the absence of the PKD gene products. Here, the authors show that the transcription factor Glis2 is a key effector of this cilia dependent cyst growth pathway and a potential target for therapy in ADPKD
- Chao Zhang
- , Michael Rehman
- & Stefan Somlo
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Article
| Open AccessGalectin-3 impairs calcium transients and β-cell function
Galectin-3, mainly produced and secreted by macrophages, is elevated in diabetes. Here, the authors show that galectin-3 directly interacts with voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and blocks calcium transients and subsequent insulin secretion.
- Qian Jiang
- , Qijin Zhao
- & Pingping Li
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Article
| Open AccessMetaboAnalystR 4.0: a unified LC-MS workflow for global metabolomics
Several bottlenecks exist in metabolomics data analysis. Here, the authors present MetaboAnalystR 4.0 as a unified workflow for LC-MS untargeted metabolomics. It highlights significant improvements in LC-MS2 spectral processing and functional analysis, providing an end-to-end computational pipeline.
- Zhiqiang Pang
- , Lei Xu
- & Jianguo Xia
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