Systems Biology
Foreign body granuloma development after calcium hydroxylapatite injection for stress urinary incontinence: A literature review and case report
Arab J Urol. 2022 Nov 15;21(2):118-125. doi: 10.1080/2090598X.2022.2146859. eCollection 2023.
ABSTRACT
OBJECTIVES: To present a case of foreign body granuloma (FBG) development after injection of calcium hydroxylapatite as a urethral bulking agent and to review all documented cases of this phenomenon in the literature.
METHODS: We analyzed a new case of calcium hydroxylapatite-induced FBG. We also conducted a literature review of the PubMed, Embase, CINAHL, and Web of Science databases through March 2022. Reports were included if they contained stress urinary incontinence patients that developed an FBG after calcium hydroxylapatite injection. The cases were reviewed for presenting symptoms, patient demographics, granuloma details, and surgical treatment.
RESULTS: We screened 250 articles and included six articles between 2006 and 2015 in addition to the present case. The median age of the patients was 65.5 years (range 45-93), and all patients were female. The most common presenting symptoms and the proportion of patients affected were difficulty voiding (4/8), recurrent urinary incontinence (3/8), and dyspareunia (2/8). The median time between the first CaHA injection and discovery of the FBG was 5 months (range 1-50). The median longest dimension of the FBGs was 1.85 cm (range 1.0-3.0). The 8 masses observed were evenly distributed throughout the urethra, with 3 in the bladder neck, 2 in the midurethra, and 3 in the distal urethra. Surgical excision was the predominant management choice, with some variation in technique.
CONCLUSIONS: Severe, persistent lower urinary tract symptoms after calcium hydroxylapatite injection may indicate an FBG, which has been successfully managed with surgical excision.
PMID:37234676 | PMC:PMC10208123 | DOI:10.1080/2090598X.2022.2146859
In Response to "Acute Renal Failure after <em>Amanita ovoidea</em> Eating"
Indian J Nephrol. 2023 Mar-Apr;33(2):155-156. doi: 10.4103/ijn.ijn_357_21. Epub 2023 Feb 20.
NO ABSTRACT
PMID:37234444 | PMC:PMC10208529 | DOI:10.4103/ijn.ijn_357_21
Editorial: The role of micronutrients in renal physiology and pathophysiology
Front Physiol. 2023 May 10;14:1207279. doi: 10.3389/fphys.2023.1207279. eCollection 2023.
NO ABSTRACT
PMID:37234425 | PMC:PMC10206295 | DOI:10.3389/fphys.2023.1207279
Deciphering the tumour immune microenvironment cell by cell
Immunooncol Technol. 2023 Apr 7;18:100383. doi: 10.1016/j.iotech.2023.100383. eCollection 2023 Jun.
ABSTRACT
Immune checkpoint inhibitors (ICIs) have rejuvenated therapeutic approaches in oncology. Although responses tend to be durable, response rates vary in many cancer types. Thus, the identification and validation of predictive biomarkers is a key clinical priority, the answer to which is likely to lie in the tumour microenvironment (TME). A wealth of data demonstrates the huge impact of the TME on ICI response and resistance. However, these data also reveal the complexity of the TME composition including the spatiotemporal interactions between different cell types and their dynamic changes in response to ICIs. Here, we briefly review some of the modalities that sculpt the TME, in particular the metabolic milieu, hypoxia and the role of cancer-associated fibroblasts. We then discuss recent approaches to dissect the TME with a focus on single-cell RNA sequencing, spatial transcriptomics and spatial proteomics. We also discuss some of the clinically relevant findings these multi-modal analyses have yielded.
PMID:37234284 | PMC:PMC10206805 | DOI:10.1016/j.iotech.2023.100383
Novel Indole-Pyrazole Hybrids as Potential Tubulin-Targeting Agents; Synthesis, antiproliferative evaluation, and molecular modeling studies
J Mol Struct. 2023 Aug 5;1285:135477. doi: 10.1016/j.molstruc.2023.135477. Epub 2023 Mar 31.
ABSTRACT
Structurally diverse indole-3-pyrazole-5-carboxamide analogues (10-29) were designed, synthesized, and evaluated for their antiproliferative activity against three cancer cell lines (Huh7, MCF-7, and HCT116) using the sulforhodamine B assay. Some of the derivatives showed anticancer activities equal to or better than sorafenib against cancer cell lines. Compounds 18 showed potent activity against the hepatocellular cancer (HCC) cell lines, with IC50 values in the range 0.6-2.9 μM. Compound 18 also exhibited moderate inhibitory activity against tubulin polymerization (IC50 = 19 μM). Flow cytometric analysis of cultured cells treated with 18 also demonstrated that the compound caused cell cycle arrest at the G2/M phase in both Huh7 and Mahlavu cells and induced apoptotic cell death in HCC cells. Docking simulations were performed to determine possible modes of interaction between 18 and the colchicine site of tubulin and quantum mechanical calculations were performed to observe the electronic nature of 18 and to support docking results.
PMID:37234266 | PMC:PMC10208593 | DOI:10.1016/j.molstruc.2023.135477
Microbial biogeochemical cycling reveals the sustainability of the rice-crayfish co-culture model
iScience. 2023 Apr 26;26(5):106769. doi: 10.1016/j.isci.2023.106769. eCollection 2023 May 19.
ABSTRACT
Aquaculture has great potential in nourishing the global growing population, while such staggering yields are coupled with environmental pollution. Rice-crayfish co-culture models (RCFP) have been widely adopted in China due to their eco-friendliness. However, little is known about RCFP's microbiome pattern, which hinders our understanding of its sustainability. This study has conducted metagenomic analysis across aquaculture models and habitats, which revealed aquaculture model-specific biogeochemical cycling pattern (e.g., nitrogen (N), sulfur (S), and carbon (C)): RCFP is advantageous in N-assimilation, N-contamination, and S-pollutants removal, while non-RCFP features N denitrification process and higher S metabolism ability, producing several hazardous pollutants in non-RCFP (e.g., nitric oxide, nitrogen monoxide, and sulfide). Moreover, RCFP has greater capacity for carbohydrate enzyme metabolism compared with non-RCFP in environmental habitats, but not in crayfish gut. Collectively, RCFP plays an indispensable role in balancing aquaculture productivity and environmental protection, which might be applied to the blue transformation of aquaculture.
PMID:37234090 | PMC:PMC10206492 | DOI:10.1016/j.isci.2023.106769
Modeling breast cancer proliferation, drug synergies, and alternating therapies
iScience. 2023 Apr 23;26(5):106714. doi: 10.1016/j.isci.2023.106714. eCollection 2023 May 19.
ABSTRACT
Estrogen receptor positive (ER+) breast cancer is responsive to a number of targeted therapies used clinically. Unfortunately, the continuous application of targeted therapy often results in resistance, driving the consideration of combination and alternating therapies. Toward this end, we developed a mathematical model that can simulate various mono, combination, and alternating therapies for ER + breast cancer cells at different doses over long time scales. The model is used to look for optimal drug combinations and predicts a significant synergism between Cdk4/6 inhibitors in combination with the anti-estrogen fulvestrant, which may help explain the clinical success of adding Cdk4/6 inhibitors to anti-estrogen therapy. Furthermore, the model is used to optimize an alternating treatment protocol so it works as well as monotherapy while using less total drug dose.
PMID:37234088 | PMC:PMC10206440 | DOI:10.1016/j.isci.2023.106714
Instrumental Drift in Untargeted Metabolomics: Optimizing Data Quality with Intrastudy QC Samples
Metabolites. 2023 May 16;13(5):665. doi: 10.3390/metabo13050665.
ABSTRACT
Untargeted metabolomics is an important tool in studying health and disease and is employed in fields such as biomarker discovery and drug development, as well as precision medicine. Although significant technical advances were made in the field of mass-spectrometry driven metabolomics, instrumental drifts, such as fluctuations in retention time and signal intensity, remain a challenge, particularly in large untargeted metabolomics studies. Therefore, it is crucial to consider these variations during data processing to ensure high-quality data. Here, we will provide recommendations for an optimal data processing workflow using intrastudy quality control (QC) samples that identifies errors resulting from instrumental drifts, such as shifts in retention time and metabolite intensities. Furthermore, we provide an in-depth comparison of the performance of three popular batch-effect correction methods of different complexity. By using different evaluation metrics based on QC samples and a machine learning approach based on biological samples, the performance of the batch-effect correction methods were evaluated. Here, the method TIGER demonstrated the overall best performance by reducing the relative standard deviation of the QCs and dispersion-ratio the most, as well as demonstrating the highest area under the receiver operating characteristic with three different probabilistic classifiers (Logistic regression, Random Forest, and Support Vector Machine). In summary, our recommendations will help to generate high-quality data that are suitable for further downstream processing, leading to more accurate and meaningful insights into the underlying biological processes.
PMID:37233706 | DOI:10.3390/metabo13050665
A Holistic Approach from Systems Biology Reveals the Direct Influence of the Quorum-Sensing Phenomenon on <em>Pseudomonas aeruginosa</em> Metabolism to Pyoverdine Biosynthesis
Metabolites. 2023 May 16;13(5):659. doi: 10.3390/metabo13050659.
ABSTRACT
Computational modeling and simulation of biological systems have become valuable tools for understanding and predicting cellular performance and phenotype generation. This work aimed to construct, model, and dynamically simulate the virulence factor pyoverdine (PVD) biosynthesis in Pseudomonas aeruginosa through a systemic approach, considering that the metabolic pathway of PVD synthesis is regulated by the quorum-sensing (QS) phenomenon. The methodology comprised three main stages: (i) Construction, modeling, and validation of the QS gene regulatory network that controls PVD synthesis in P. aeruginosa strain PAO1; (ii) construction, curating, and modeling of the metabolic network of P. aeruginosa using the flux balance analysis (FBA) approach; (iii) integration and modeling of these two networks into an integrative model using the dynamic flux balance analysis (DFBA) approximation, followed, finally, by an in vitro validation of the integrated model for PVD synthesis in P. aeruginosa as a function of QS signaling. The QS gene network, constructed using the standard System Biology Markup Language, comprised 114 chemical species and 103 reactions and was modeled as a deterministic system following the kinetic based on mass action law. This model showed that the higher the bacterial growth, the higher the extracellular concentration of QS signal molecules, thus emulating the natural behavior of P. aeruginosa PAO1. The P. aeruginosa metabolic network model was constructed based on the iMO1056 model, the P. aeruginosa PAO1 strain genomic annotation, and the metabolic pathway of PVD synthesis. The metabolic network model included the PVD synthesis, transport, exchange reactions, and the QS signal molecules. This metabolic network model was curated and then modeled under the FBA approximation, using biomass maximization as the objective function (optimization problem, a term borrowed from the engineering field). Next, chemical reactions shared by both network models were chosen to combine them into an integrative model. To this end, the fluxes of these reactions, obtained from the QS network model, were fixed in the metabolic network model as constraints of the optimization problem using the DFBA approximation. Finally, simulations of the integrative model (CCBM1146, comprising 1123 reactions and 880 metabolites) were run using the DFBA approximation to get (i) the flux profile for each reaction, (ii) the bacterial growth profile, (iii) the biomass profile, and (iv) the concentration profiles of metabolites of interest such as glucose, PVD, and QS signal molecules. The CCBM1146 model showed that the QS phenomenon directly influences the P. aeruginosa metabolism to PVD biosynthesis as a function of the change in QS signal intensity. The CCBM1146 model made it possible to characterize and explain the complex and emergent behavior generated by the interactions between the two networks, which would have been impossible to do by studying each system's individual components or scales separately. This work is the first in silico report of an integrative model comprising the QS gene regulatory network and the metabolic network of P. aeruginosa.
PMID:37233700 | DOI:10.3390/metabo13050659
Human Metabolome Reference Database in a Biracial Cohort across the Adult Lifespan
Metabolites. 2023 Apr 25;13(5):591. doi: 10.3390/metabo13050591.
ABSTRACT
As one of the OMICS in systems biology, metabolomics defines the metabolome and simultaneously quantifies numerous metabolites that are final or intermediate products and effectors of upstream biological processes. Metabolomics provides accurate information that helps determine the physiological steady state and biochemical changes during the aging process. To date, reference values of metabolites across the adult lifespan, especially among ethnicity groups, are lacking. The "normal" reference values according to age, sex, and race allow the characterization of whether an individual or a group deviates metabolically from normal aging, encompass a fundamental element in any study aimed at understanding mechanisms at the interface between aging and diseases. In this study, we established a metabolomics reference database from 20-100 years of age from a biracial sample of community-dwelling healthy men and women and examined metabolite associations with age, sex, and race. Reference values from well-selected healthy individuals can contribute to clinical decision-making processes of metabolic or related diseases.
PMID:37233632 | DOI:10.3390/metabo13050591
Influence of Membrane Asymmetry on OmpF Insertion, Orientation and Function
Membranes (Basel). 2023 May 16;13(5):517. doi: 10.3390/membranes13050517.
ABSTRACT
The effect of asymmetric membranes containing lipopolysaccharides (LPS) on the outer membrane protein F (OmpF) reconstitution, channel orientation, and antibiotic permeation across the outer membrane was investigated. After forming an asymmetric planar lipid bilayer composed of LPS on one and phospholipids on the other side, the membrane channel OmpF was added. The ion current recordings demonstrate that LPS has a strong influence on the OmpF membrane insertion, orientation, and gating. Enrofloxacin was used as an example of an antibiotic interacting with the asymmetric membrane and with OmpF. The enrofloxacin caused the blockage of the ion current through the OmpF, depending on the side of addition, the transmembrane voltage applied, and the composition of the buffer. Furthermore, the enrofloxacin changed the phase behavior of the LPS-containing membranes, demonstrating that its membrane activity influences the function of OmpF and potentially the membrane permeability.
PMID:37233578 | DOI:10.3390/membranes13050517
Coccidioidomycosis and Host Microbiome Interactions: What We Know and What We Can Infer from Other Respiratory Infections
J Fungi (Basel). 2023 May 18;9(5):586. doi: 10.3390/jof9050586.
ABSTRACT
Between 70 and 80% of Valley fever patients receive one or more rounds of antibiotic treatment prior to accurate diagnosis with coccidioidomycosis. Antibiotic treatment and infection (bacterial, viral, fungal, parasitic) often have negative implications on host microbial dysbiosis, immunological responses, and disease outcome. These perturbations have focused on the impact of gut dysbiosis on pulmonary disease instead of the implications of direct lung dysbiosis. However, recent work highlights a need to establish the direct effects of the lung microbiota on infection outcome. Cystic fibrosis, chronic obstructive pulmonary disease, COVID-19, and M. tuberculosis studies suggest that surveying the lung microbiota composition can serve as a predictive factor of disease severity and could inform treatment options. In addition to traditional treatment options, probiotics can reverse perturbation-induced repercussions on disease outcomes. The purpose of this review is to speculate on the effects perturbations of the host microbiome can have on coccidioidomycosis progression. To do this, parallels are drawn to aa compilation of other host microbiome infection studies.
PMID:37233297 | DOI:10.3390/jof9050586
Online bias-aware disease module mining with ROBUST-Web
Bioinformatics. 2023 May 26:btad345. doi: 10.1093/bioinformatics/btad345. Online ahead of print.
ABSTRACT
SUMMARY: We present ROBUST-Web which implements our recently presented ROBUST disease module mining algorithm in a user-friendly web application. ROBUST-Web features seamless downstream disease module exploration via integrated gene set enrichment analysis, tissue expression annotation, and visualization of drug-protein and disease-gene links. Moreover, ROBUST-Web includes bias-aware edge costs for the underlying Steiner tree model as a new algorithmic feature, which allow to correct for study bias in protein-protein interaction networks and further improves the robustness of the computed modules.
AVAILABILITY AND IMPLEMENTATION: Web application: https://robust-web.net. Source code of web application and Python package with new bias-aware edge costs: https://github.com/bionetslab/robust-web, https://github.com/bionetslab/robust_bias_aware.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
PMID:37233198 | DOI:10.1093/bioinformatics/btad345
Eternal nodules to fix the nitrogen issue: Promotion of soybean nodule senescence by a NAC/CYP module
Plant Cell. 2023 May 26:koad154. doi: 10.1093/plcell/koad154. Online ahead of print.
NO ABSTRACT
PMID:37233028 | DOI:10.1093/plcell/koad154
High-Throughput Analysis of Underivatized Amino Acids and Acylcarnitines in Infant Serum: A Micromethod Based on Stable Isotope Dilution Targeted HILIC-ESI-MS/MS
J Agric Food Chem. 2023 May 26. doi: 10.1021/acs.jafc.3c00962. Online ahead of print.
ABSTRACT
Amino acids and acylcarnitines are important biomarkers of the body's energy state and can be used as diagnostic markers of certain inborn errors of metabolism. Few multianalyte methods for high-throughput analysis in serum exist for these compounds, but micromethods suitable for use in young children and infants are lacking. Therefore, we developed a quantitative high-throughput multianalyte hydrophilic interaction liquid chromatography-tandem mass spectrometry method preceded by a derivatization-free sample preparation using minimum amounts of serum (25 μL). Isotopically labeled standards were utilized for quantification. Forty amino acids and amino acid derivatives and 22 acylcarnitines were detected by applying a multiple reaction monitoring mode within a 20 min run. The method was comprehensively validated, comprising linearity, accuracy, (intraday/interday) precision, and quantitation limits, of which the latter ranged from 0.25 to 50 nM for acylcarnitines and from 0.005 to 1 μM for amino acids and their derivatives. Application of the method to 145 serum samples of three- to four-month-old healthy infants showed excellent reproducibility for multiday analyses and enabled simultaneous amino acid and acylcarnitine profiling in this age group.
PMID:37232935 | DOI:10.1021/acs.jafc.3c00962
The Effect of Lung Resection for NSCLC on Circulating Immune Cells: A Pilot Study
Curr Oncol. 2023 May 17;30(5):5116-5134. doi: 10.3390/curroncol30050387.
ABSTRACT
This pilot study sought to evaluate the circulating levels of immune cells, particularly regulatory T-cell (Treg) subsets, before and after lung resection for non-small cell lung cancer. Twenty-five patients consented and had specimens collected. Initially, peripheral blood of 21 patients was collected for circulating immune cell studies. Two of these patients were excluded due to technical issues, leaving 19 patients for the analyses of circulating immune cells. Standard gating and high-dimensional unsupervised clustering flow cytometry analyses were performed. The blood, tumors and lymph nodes were analyzed via single-cell RNA and TCR sequencing for Treg analyses in a total of five patients (including four additional patients from the initial 21 patients). Standard gating flow cytometry revealed a transient increase in neutrophils immediately following surgery, with a variable neutrophil-lymphocyte ratio and a stable CD4-CD8 ratio. Unexpectedly, the total Treg and Treg subsets did not change with surgery with standard gating in short- or long-term follow-up. Similarly, unsupervised clustering of Tregs revealed a dominant cluster that was stable perioperatively and long-term. Two small FoxP3hi clusters slightly increased following surgery. In the longer-term follow-up, these small FoxP3hi Treg clusters were not identified, indicating that they were likely a response to surgery. Single-cell sequencing demonstrated six CD4+FoxP3+ clusters among the blood, tumors and lymph nodes. These clusters had a variable expression of FoxP3, and several were mainly, or only, present in tumor and lymph node tissue. As such, serial monitoring of circulating Tregs may be informative, but not completely reflective of the Tregs present in the tumor microenvironment.
PMID:37232845 | DOI:10.3390/curroncol30050387
Pressure-dependent growth controls 3D architecture of Pseudomonas putida microcolonies
Environ Microbiol Rep. 2023 May 25. doi: 10.1111/1758-2229.13182. Online ahead of print.
ABSTRACT
Colony formation is key to many ecological and biotechnological processes. In its early stages, colony formation involves the concourse of a number of physical and biological parameters for generation of a distinct 3D structure-the specific influence of which remains unclear. We focused on a thus far neglected aspect of the process, specifically the consequences of the differential pressure experienced by cells in the middle of a colony versus that endured by bacteria located in the growing periphery. This feature was characterized experimentally in the soil bacterium Pseudomonas putida. Using an agent-based model we recreated the growth of microcolonies in a scenario in which pressure was the only parameter affecting proliferation of cells. Simulations exposed that, due to constant collisions with other growing bacteria, cells have virtually no free space to move sideways, thereby delaying growth and boosting chances of overlapping on top of each other. This scenario was tested experimentally on agar surfaces. Comparison between experiments and simulations suggested that the inside/outside differential pressure determines growth, both timewise and in terms of spatial directions, eventually moulding colony shape. We thus argue that-at least in the case studied-mere physical pressure of growing cells suffices to explain key dynamics of colony formation.
PMID:37231623 | DOI:10.1111/1758-2229.13182
Gene network analysis of oxaliplatin-resistant colorectal cancer to target a crucial gene using chitosan/hyaluronic acid/protamine polyplexes containing CRISPR-Cas9
Biochim Biophys Acta Gen Subj. 2023 May 23:130385. doi: 10.1016/j.bbagen.2023.130385. Online ahead of print.
ABSTRACT
Colorectal cancer (CRC) treatment is dramatically hampered by resistance to oxaliplatin alone or in the combination of irinotecan or 5-fluorouracil and leucovorin. This study aims to design and assess Chitosan/Hyaluronic Acid/Protamine sulfate (CS/HA/PS) polyplexes loaded with CRISPR plasmid for targeting a key gene in cancer drug resistance. Here, recent findings were considered to validate oxaliplatin-resistant CRC-related genes and systems biology approaches employed to detect the critical gene. The polyplexes were characterized according to particle size, zeta potential, and stability. Moreover, carrier toxicity and transfection efficiency were assessed on oxaliplatin-resistant HT-29 cells. The post-transfection evaluations were performed to confirm gene disruption-mediated CRISPR. Eventually, excision cross complementation group 1(ERCC1), a crucial member of the nucleotide excision repair pathway, was selected to be targeted using CRISPR/Cas9 to reverse oxaliplatin resistance in HT-29 cells. CS/HA/PS polyplexes containing CRISPR/Cas9 plasmid exhibited negligible toxicity and comparable transfection efficiency with Lipofectamine™. Following the efficient gene delivery, sequences in CRISPR/Cas9 target sites were altered, ERCC1 was downregulated, and drug sensitivity was successfully restored in oxaliplatin-resistant cells. Findings indicate that CS/HA/PS/CRISPR polyplexes provide a potential strategy for delivering cargo and targeting oxaliplatin resistance-related gene to manipulate drug resistance as a rising concern in cancer therapeutic approaches.
PMID:37230419 | DOI:10.1016/j.bbagen.2023.130385
Comparison of force fields to study the zinc-finger containing protein NPL4, a target for disulfiram in cancer therapy
Biochim Biophys Acta Proteins Proteom. 2023 May 23:140921. doi: 10.1016/j.bbapap.2023.140921. Online ahead of print.
ABSTRACT
Molecular dynamics (MD) simulations are a powerful approach to studying the structure and dynamics of proteins related to health and disease. Advances in the MD field allow modeling proteins with high accuracy. However, modeling metal ions and their interactions with proteins is still challenging. NPL4 is a zinc-binding protein and works as a cofactor for p97 to regulate protein homeostasis. NPL4 is of biomedical importance and has been proposed as the target of disulfiram, a drug recently repurposed for cancer treatment. Experimental studies proposed that the disulfiram metabolites, bis-(diethyldithiocarbamate)‑copper and cupric ions, induce NPL4 misfolding and aggregation. However, the molecular details of their interactions with NPL4 and consequent structural effects are still elusive. Here, biomolecular simulations can help to shed light on the related structural details. To apply MD simulations to NPL4 and its interaction with copper the first important step is identifying a suitable force field to describe the protein in its zinc-bound states. We examined different sets of non-bonded parameters because we want to study the misfolding mechanism and cannot rule out that the zinc may detach from the protein during the process and copper replaces it. We investigated the force-field ability to model the coordination geometry of the metal ions by comparing the results from MD simulations with optimized geometries from quantum mechanics (QM) calculations using model systems of NPL4. Furthermore, we investigated the performance of a force field including bonded parameters to treat copper ions in NPL4 that we obtained based on QM calculations.
PMID:37230374 | DOI:10.1016/j.bbapap.2023.140921
Limitations and advantages of using metabolite-based genome-wide association studies: focus on fruit quality traits
Plant Sci. 2023 May 23:111748. doi: 10.1016/j.plantsci.2023.111748. Online ahead of print.
ABSTRACT
In the last decades, linkage mapping has help in the location of metabolite quantitative trait loci (QTL) in many species; however, this approach shows some limitations. Recently, thanks to the most recent advanced in high-throughput genotyping technologies like next-generation sequencing, metabolite genome-wide association study (mGWAS) has been proposed a powerful tool to identify the genetic variants in polygenic agrinomic traits. Fruit flavor is a complex interaction of aroma volatiles and taste being sugar and acid ratio key parameter for flavor acceptance. Here, we review recent progress of mGWAS in pinpoint gene polymorphisms related to flavor-related metabolites in fruits. Despite clear successes in discovering novel genes or regions associated with metabolite accumulation affecting sensory attributes in fruits, GWAS incurs in several limitations summarized in this review. In addition, in our own work, we performed mGWAS on 194 Citrus grandis accessions to investigate the genetic control of individual primary and lipid metabolites in ripe fruit. We have identified a total of 667 associations for 14 primary metabolites including amino acids, sugars, and organic acids, and 768 associations corresponding to 47 lipids. Furthermore, candidate genes related to important metabolites related to fruit quality such as sugars, organic acids and lipids were discovered.
PMID:37230189 | DOI:10.1016/j.plantsci.2023.111748