Biology subjects

Liu, P.

Publications and source records attributed to Liu, P..

At least 235 records · Page 13Linked to original sources

bioRxiv2022

Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents

SARS-CoV-2 Omicron sublineages have escaped most RBD-targeting therapeutic neutralizing antibodies (NAbs), which proves the previous NAb drug screening strategies deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following the criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection. Our screening strategy can also be applied to identify broad-spectrum NAb drugs against other fast-evolving viruses, such as influenza viruses.

immunology↗

bioRxiv2022

Low photosynthetic rate under low light stress inhibited sucrose distribution and transportation to grain

Under the condition of low light, the yield of summer maize decreased significantly, but the decrease of yield under low light stress was not only caused by the lack of photosynthetic assimilates in leaves, but also the transportation and utilization of assimilates by stems and grains. In this study, we investigated the effects of low light stress on leaves, stems and grains of summer maize and the relationship between them. The results showed that the synthesis ability of sucrose and export sucrose to grains ability in leaves decreased under low light. Due to dry matter transfer, the number and area of small vascular bundles in spike node and shank decreased, which restricted the translocation of photoassimilates to grains at filling stage. The activities of SUS and AGPase was decreased in grains under low light stress, which limited the availability of sucrose. The process of leaf synthesis, sucrose loading and sucrose utilization in grains was affected under low light, resulting in relatively higher sucrose concentration in grains than in leaves, forming a "leaf low" - "grain high" sugar concentration gradient, resulting in the opposite hydrostatic pressure, and then feedback inhibition of sucrose output in leaves, reducing sucrose loading and transportation rate. HightlightThe key factor of low light stress reducing summer maize yield was the decrease of leaf photosynthetic rate, resulting in insufficient grain dry matter supply. The sugar concentration gradient between leaves and grains further restricted the sucrose transport from leaves to grains.

plant biology↗

bioRxiv2022

The 3D Structural Architecture of the Human Hand Area is Non-Topographic

The functional topography of the human primary somatosensory cortex (S1) hand area is a widely studied model system to understand sensory organization and plasticity. It is so far unclear whether or not the underlying 3D structural architecture also shows a topographic organization. We used 7T MRI data to quantify layer-specific myelin, iron and mineralization in relation to population receptive field maps of individual finger representations in Brodman area 3b (BA 3b) of human S1 in female and male younger adults. This 3D description allowed us to identify a characteristic profile of layer-specific myelin and iron deposition in the BA 3b hand area, but revealed an absence of structural differences, an absence of low-myelin borders, and high similarity of 3D microstructure profiles between individual fingers. However, structural differences and borders were detected between the hand and face areas. We conclude that the 3D structural architecture of the human hand area is non-topographic, unlike in some monkey species, which suggests a high degree of flexibility for functional finger organization and a new perspective on human topographic plasticity. Significance StatementUsing ultra-high field MRI, we provide the first comprehensive in vivo description of the 3D structural architecture of the human BA 3b hand area in relation to functional population receptive field (pRF) maps. High similarity of precise finger-specific 3D profiles, together with an absence of structural differences and an absence of low-myelin borders between individual fingers, reveal the 3D structural architecture of the human hand area to be non-topographic. This suggests reduced structural limitations to cortical plasticity and reorganization, and allows for shared representational features across fingers.

neuroscience↗

bioRxiv2022

AGC Kinase Inhibitors Regulate STING Signaling Through SGK-Dependent and SGK-Independent Mechanisms

The STING signaling pathway is essential for the innate immune response to DNA viruses and bacteria and is important in tumor immunity. STING binding to cGAMP or to synthetic agonists leads to the activation of the kinase TBK1 which phosphorylates the transcription factor IRF3 which promotes expression of type 1 interferons such as IFN{beta} to block viral activity. Aberrant type 1 IFN expression is associated with human diseases including autoimmunity, HIV, and cancer. Here we identify N-[4-(1H-pyrazolo[3,4-b] pyrazin-6-yl)-phenyl]-sulfonamide (Sanofi-14h), a compound with preference for inhibition of the AGC family kinase SGK3, as an inhibitor of IFN{beta} gene expression in response to STING stimulation of macrophages. Sanofi-14h abrogated SGK activity and also impaired activation of the critical TBK1/IRF3 pathway downstream of STING activation, notably blocking the ligand-induced interaction of STING with TBK1. Deletion of SGK1 and SGK3 in macrophages suppressed activation of IFN{beta} transcription but did not block TBK1/IRF3 activation downstream of STING. Gene and protein expression analysis revealed that deletion of SGK1/3 in a macrophage cell line decreases basal expression of critical transcription factors required for the innate immune response, such as IRF7 and STAT1. Additional studies reveal that other AGC kinase inhibitors block TBK1 and IRF3 activation suggesting common action on a critical regulatory node in the STING pathway. Thus, studies with Sanofi-14h have revealed both SGK-dependent and SGK-independent effects in the STING pathway and suggest a mechanism to alter type 1 IFN transcription through small molecule therapy.

immunology↗

bioRxiv2022

Using colony size to measure fitness in Saccharomyces cerevisiae

Competitive fitness assays in liquid culture have been a mainstay for characterizing experimental evolution of microbial populations. Growth of microbial strains has also been extensively characterized by colony size and could serve as a useful alternative if translated to per generation measurements of relative fitness. To examine fitness based on colony size, we established a relationship between cell number and colony size for strains of Saccharomyces cerevisiae robotically pinned onto solid agar plates in a high-density format. This was used to measure growth rates and estimate relative fitness differences between evolved strains and their ancestors. After controlling for edge effects through both normalization and agar-trimming, we found that fitness based on colony size is as sensitive as competitive fitness assays grown in liquid medium. While fitnesses determined from liquid and solid mediums were not equivalent, our results demonstrate that colony size provides a sensitive means of measuring fitness that is particularly well suited to measurements across many environments.

evolutionary biology↗

bioRxiv2022

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

Emerging severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, especially the Omicron variant, have impaired the efficacy of existing vaccines and most therapeutic antibodies, highlighting the need for additional antibody-based tools that can efficiently neutralize emerging SARS-CoV-2 variants. The use of a "single" agent to simultaneously target multiple distinct epitopes on the spike is desirable to overcome the neutralizing escape of SARS-CoV-2 variants. Herein, we generated a human-derived IgG-like bispecific antibody (bsAb), Bi-Nab35B5-47D10, which successfully retained the specificity and simultaneously bound to the two distinct epitopes on RBD and S2. Bi-Nab35B5-47D10 showed improved spike binding breadth among wild-type (WT) SARS-CoV-2, variants of concern (VOCs) and variants being monitored (VBMs) compared with its parental mAbs. Furthermore, pseudotyped virus neutralization demonstrated that Bi-Nab35B5-47D10 can efficiently neutralize VBMs including Alpha (B.1.1.7), Beta (B.1.351) and Kappa (B.1.617.1) and VOCs including Delta (B.1.617.2), Omicron BA.1 and Omicron BA.2. Crucially, Bi-Nab35B5-47D10 substantially improved neutralizing activity against Omicron BA.1 (IC50= 27.3 ng/mL) and Omicron BA.2 (IC50= 121.1 ng/mL) compared with their parental mAbs. Therefore, Bi-Nab35B5-47D10 represents a potential effective countermeasure against SARS-CoV-2 Omicron and other variants of concern. ImportanceThe new highly contagious SARS-CoV-2 Omicron variant caused substantial breakthrough infections and has become the dominant strain in countries across the world. Omicron variants usually bear high mutations in the spike protein and exhibit considerable escape of most potent neutralization monoclonal antibodies and reduced efficacy of current COVID-19 vaccines. The development of neutralizing antibodies with potent efficacy against the Omicron variant is still an urgent priority. Here, we generated a bsAb, Bi-Nab35B5-47D10, that simultaneously targets SARS-CoV-2 RBD and S2 and improved neutralizing potency and breadth against SARS-CoV-2 WT and the tested variants compared with their parental antibodies. Notably, Bi-Nab35B5-47D10 has more potent neutralizing activity against the VOC Omicron pseudotyped virus. Therefore, Bi-Nab35B5-47D10 is a feasible and potentially effective strategy to treat and prevent COVID-19.

immunology↗

bioRxiv2022

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles

Activation of voltage-gated calcium channels at synapses leads to local increases in calcium and the fusion of synaptic vesicles. However, presynaptic output will be determined by the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at C. elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters [~]300 nm in diameter with the active zone proteins Neurexin, -Liprin, SYDE, ELKS/CAST, RIM-BP, -Catulin, and MAGI1. CaV2 channels mediate the fusion of vesicles docked adjacent to the dense projection and are colocalized with the synaptic vesicle priming protein UNC-13L. By contrast, CaV1 channels are dispersed in the synaptic varicosity and are coupled to internal calcium stores via the ryanodine receptor. CaV1 and ryanodine receptor mediate the fusion of vesicles docked broadly in the synaptic varicosity and are colocalized with the vesicle priming protein UNC-13S. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.

neuroscience↗

bioRxiv2022

BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

immunology↗

bioRxiv2022

Thermophoresis of Molecules and Structures of different Sizes in Self-assembled Biomatrices

Upon subjecting biomolecules to non-equilibrium conditions, many biochemical and biophysical features such as biomolecular diffusion, protein folding, interaction kinetics, as well as enzyme-catalyzed reactions can be characterized in an aqueous solution. However, most assays under non-equilibrium conditions cannot be performed in complex self-assembled biomatrices (e.g. extracellular matrices) due to the limitations associated with sample handling, reaction design, and optical detection. Herein, we report the study of biomolecular thermodiffusion in non-covalently assembled synthetic or naturally derived hydrogels. This approach has been demonstrated with a large variety of analytes, including small molecules, polysaccharides, DNAs, DNA origami, and proteins in various polymer networks. The in-biomatrix method has also shown advantages over in-solution measurements: First, it allows us to analyze biomolecules in 3D matrices in a high-throughput fashion. Second, the aggregation of analytes can be remarkably prevented. Although the underlying physics of thermodiffusion is still not well-understood, we demonstrated that the thermodiffusion of surrounding networks will enhance the thermodiffusion of the analyte, an effect counteracting the hindered movement by the polymer network.

biophysics↗

bioRxiv2022

Identification of YAB11-NGAL1 controlling leaf serrations through enhanced genome-wide association studies of Populus

Leaf margins are complex plant morphological features and contribute to the diversity of leaf shapes which effect on plant structure, yield and adaptation. Although several regulators of leaf margins have been identified, the genetic basis of natural variation therein has not been fully elucidated. We first profiled two distinct types (serration and smooth) of leaf morphology using the persistent homology mathematical framework (PHMF) in poplar. Combined genome-wide association studies (GWAS) and expression quantitative trait nucleotide (eQTN) mapping to create a module of leaf morphology controlling using data from Populus tomentosa and P. simonii association population, respectively. Natural variation of leaf margins is associated with transcript abundances of YABBY11 (YAB11) in poplar. In P. tomentosa, PtoYAB11 carries premature stop codon (PtoYAB11PSC) resulting in lost its positive regulation in PtoNGAL-1, PtoRBCL, PtoATPA, PtoATPE, and PtoPSBB. Overexpression of PtoYAB11PSC serrated leaf margin, enlarged leaves, promoted photosynthesis and increased biomass. Overexpression of PsiYAB11 in P. tomentosa could rescue leaf margin serration and increase stomatal density and light damage repair ability. In poplar, YAB11-NGAL1is sensitive to environmental conditions and play positive regulator of leaf margin serration. It might be important regulator which bridge environment signaling to leaf morphological plasticity.

plant biology↗

bioRxiv2022

Enhancing Prime Editing Efficiency and Flexibility with Tethered and Split pegRNAs

Prime editing (PE) has advantages for small insertion, deletion or point mutations without double-stranded DNA breaks. The 3-extension of pegRNAs could negatively affect its stability or folding and comprise the PE activity. Here we generated stem-loop PEs (sPEs) by adding stem-loop aptamers at the 3-terminal of pegRNA, which can be tethered to Cas9 nickase resulting in tethered PEs (tPEs). sPEs and tPEs increased the small insertion, deletion or point mutations efficiency by 2-4-fold on average in HEK293, U2OS and HeLa cells. We split the modified pegRNAs into sgRNA and prime RNA. The resulting split pegRNA prime editors (SnPEs) maintain the PE activity and increase flexibility.

molecular biology↗

bioRxiv2022

Interrogating Metabolic Interactions Between Skeletal Muscle and Liver Circadian Clocks In Vivo

Expressed throughout the body, the circadian clock system achieves daily metabolic homeostasis at every level of physiology, with clock disruption associated with metabolic disease (1, 2). Molecular clocks present in the brain, liver, adipose, pancreas and skeletal muscle each contribute to glucose homeostasis (3). However, it is unclear; 1) which organ clocks provide the most essential contributions, and 2) if these contributions depend on inter-organ communication. We recently showed that the liver clock alone is insufficient for most aspects of daily liver glucose handling and requires connections with other clocks (4). Considering the pathways that link glucose metabolism between liver and skeletal muscle, we sought to test whether a clock connection along this axis is important. Using our previous published methodology for tissue-specific rescue of Bmal1 in vivo (4, 5), we now show that in the absence of feeding-fasting cycles, liver and muscle clocks are not sufficient for systemic glucose metabolism, nor do they form a functional connection influencing local glucose handling or daily transcriptional rhythms in each tissue. However, the introduction of a daily feeding-fasting rhythm enables a synergistic state between liver and muscle clocks that leads to restoration of systemic glucose tolerance. These findings reveal limited autonomous capabilities of liver and muscle clocks and highlight the need for inter-organ clock communication for glucose homeostasis which involves at least two peripheral metabolic organs.

cell biology↗

bioRxiv2022

Chlamydomonas mutant hpm91 lacking PGR5 is a scalable and valuable strain for algal hydrogen (H2) production

Clean and sustainable H2 production is essential toward a carbon-neutral world. H2 generation by Chlamydomonas reinhardtii is an attractive approach for solar-H2 from H2O. However, it is currently not scalable because of lacking ideal strains. Here, we explore hpm91, a previously reported PGR5-deletion mutant with remarkable H2 production, that possesses numerous valuable attributes towards large-scale application and in-depth study issues. We show that hpm91 is at least 100-fold scalable (upto 10 liter) with H2 collection sustained for averagely 26 days and 7287 ml H2/10L-HPBR. Also, hpm91 is robust and active over the period of sulfur-deprived H2 production, most likely due to decreased intracellular ROS relative to wild type. Moreover, quantitative proteomic analysis revealed its features in photosynthetic antenna, primary metabolic pathways and anti-ROS responses. Together with success of new high-H2-production strains derived from hpm91, we highlight that hpm91 is a potent strain toward basic and applied research of algal-H2 photoproduction.

biochemistry↗

bioRxiv2022

CRISPR-mediated correction of skeletal muscle Ca2+ handling in a novel DMD patient-derived pluripotent stem cell model

Mutations in the dystrophin gene cause the most common and currently incurable Duchenne muscular dystrophy (DMD) characterized by progressive muscle wasting. Although abnormal Ca2+ handling is a pathological feature of DMD, mechanisms underlying defective Ca2+ homeostasis remain unclear. Here we generate a novel DMD patient-derived pluripotent stem cell (PSC) model of skeletal muscle with an isogenic control using clustered regularly interspaced short palindromic repeat (CRISPR)- mediated precise gene correction. Transcriptome analysis identifies dysregulated gene sets in the absence of dystrophin, including genes involved in Ca2+ handling, excitation-contraction coupling and muscle contraction. Specifically, analysis of intracellular Ca2+ transients and mathematical modeling of Ca2+ dynamics reveal significantly reduced cytosolic Ca2+ clearance rates in DMD-PSC derived myotubes. Pharmacological assays demonstrate Ca2+ flux in myotubes is determined by both intracellular and extracellular sources. DMD-PSC derived myotubes display significantly reduced velocity of contractility. Compared with a non-isogenic wild type PSC line, these pathophysiological defects could be rescued by CRISPR-mediated precise gene correction. Our study provides new insights into abnormal Ca2+ homeostasis in DMD and suggests that Ca2+ signaling pathways amenable to pharmacological modulation are potential therapeutic targets. Importantly, we have established a human physiology-relevant in vitro model enabling rapid pre-clinical testing of potential therapies for DMD.

cell biology↗

bioRxiv2022

Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies

Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.

immunology↗

bioRxiv2022

Optimization of NLS Composition Improves CRISPR-Cas12a Editing Rates in Human Primary Cells

Type V CRISPR-Cas12a systems are an attractive alternative nuclease platform for specific genome editing applications. However, previous studies demonstrate that there is a gap in overall activity between Cas12a and Cas9 in primary cells. Here we describe optimization to the nuclear localization signal composition and architecture of Cas12a to facilitate highly efficient targeted mutagenesis in mammalian cell lines (HEK293T, Jurkat, and K562 cells) and primary cells (NK cells and CD34+ HSPCs), regardless of Cas12a ortholog. A 3xNLS Cas12a architecture resulted in the most robust editing platform. The improved editing activity of Cas12a in both NK cells and CD34+ HSPCs resulted in pronounced phenotypic changes associated with target gene editing. Lastly, we demonstrated that optimization of the NLS composition and architecture of Cas12a did not decrease the specificity of editing in HEK293T and CD34+ HSPCs. Our new Cas12a NLS variant provides an improved nuclease platform for therapeutic genome editing.

molecular biology↗

bioRxiv2022

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors1-4. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic5. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.

microbiology↗

bioRxiv2022

OrganoID: a versatile deep learning platform for organoid image analysis

Organoids have immense potential as ex vivo disease models for drug discovery and personalized drug screening. Dynamic changes in individual organoid morphology, number, and size can indicate important drug responses, however these metrics are difficult and labor-intensive to obtain for high-throughput image datasets. Here, we present OrganoID, a robust image analysis platform that automatically recognizes, labels, and tracks single organoids, pixel-by-pixel, in brightfield and phase-contrast microscopy experiments. The platform was trained on images of pancreatic cancer organoids and validated on separate images of pancreatic, lung, colon, and adenoid cystic carcinoma organoids, which showed excellent agreement with manual measurements of organoid count (96%) and size (95%) without any parameter adjustments. Single-organoid tracking accuracy remained above 89% over a four-day time-lapse microscopy study. Automated single-organoid morphology analysis of a chemotherapy dose-response experiment identified decreased organoid circularity as an important morphological feature reflecting drug response. OrganoID enables straightforward, detailed, and accurate image analysis to accelerate the use of organoids in high-throughput, data-intensive biomedical applications.

bioengineering↗