Biology subjects

Yu, S.

Publications and source records attributed to Yu, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Systematic analysis reveals an Mln1-dependent trade-off between metabolic flexibility and thermotolerance in Cryptococcus neoformans

During infection, fungal pathogens must adapt to multiple environmental challenges, including changes in temperature, nutrient availability, and immune stress. Although transcriptional regulators are central to these adaptations, how individual regulators contribute to distinct environmental responses and how these responses are functionally interconnected remain poorly understood. Here, we investigated the functions of infection-associated transcription factors under distinct host-relevant conditions in Cryptococcus neoformans. Integrating in vivo expression profiling with infectivity data from signature-tagged mutagenesis, we prioritized 24 transcription factors, 12 of which were induced under host-mimicking conditions. Initial functional analyses revealed distinct roles for these transcription factors in adaptation to temperature, carbon, and nitrogen availability. Further characterization of Mln1, a fungal basic helix-loop-helix transcription factor, uncovered an unexpected connection between carbon source adaptation and thermotolerance. Mig1-dependent repression limited MLN1 expression in the presence of glucose, whereas Mln1 accumulated in the nucleus in the presence of trehalose or ethanol, but not glucose. Loss of MLN1 impaired carbon-starvation gene expression and growth on non-preferred carbon sources, particularly trehalose. Conversely, mln1{Delta} cells accumulated more intracellular trehalose and exhibited enhanced thermotolerance, yet showed reduced melanization, titan cell formation, virulence in Drosophila, and brain fungal burden in mice. Together, these results suggest that Mln1 contributes to metabolic flexibility and fungal virulence while differentially influencing thermotolerance. More broadly, these findings highlight a potential physiological trade-off between nutrient utilization and stress resistance, suggesting that these adaptive processes may be interconnected in fungal pathogens.

microbiology↗

bioRxiv2026

Stabilizing gas in aqueous liquids with metal-organic frameworks for persistent acoustic transduction

Gas is the most efficient mediator of acoustic energy owing to its high compressibility, yet its thermodynamic instability in aqueous environments makes it inherently transient, limiting sustained ultrasound-biological interfacing. Here, we show that gas can be stabilized, confined, and manipulated in the liquid phase to function as a persistent acoustic transducer. By trapping gas within designed microporous metal-organic framework (MOF) nanocrystals, interfacial forces establish a stable ternary-phase equilibrium that suppresses water intrusion and prevents gas collapse, enabling reversible, non-destructive oscillations under ultrasound stimulation and providing design principles for stabilizing gas in liquid environments. By leveraging high-resolution ultra-high-speed digital image correlation (DIC), we unveil the previously inaccessible spatiotemporal dynamics of confined gas oscillations within these nanotransducers under ultrasound stimulation, revealing localized amplification of the surrounding acoustic field and establishing a quantitative structure-function relationship for programmable acoustic transduction. These aqueous-phase gas nanotransducers exhibit sustained acoustic amplification over millions of excitation cycles and remain functional after prolonged storage (>2 years) under physiological conditions. In vitro and in vivo, this platform enables long-term ultrasound imaging and sustained, non-invasive neuromodulation by converting confined gas oscillations into persistent and amplified mechanical actuation. Our findings establish a generalizable design framework for stabilizing gas in liquid environments to achieve persistent and programmable acoustic transduction, thereby enabling sustained ultrasound-biological interfacing and opening opportunities for gas-based therapeutics.

bioengineering↗

bioRxiv2026

Excluded Volume Effect-induced Shrinkage for Resolution Enhancement of Hydrogel Bioconstructs

Biofabrication of hydrogel materials is usually constrained by process-specific resolution limits. Here, we introduce excluded volume effect-induced shrinkage (EVER), a dehydration-enabled resolution enhancement strategy that achieves dimensional refinement via post-processing. In this approach, we treat biofabricated constructs with hydrophilic macromolecular crowding agent bath, with poloxamer as a representative. With EVER treatment, gelatin-based constructs can reach a dimension reduction of up to ~49% with an estimated volumetric reduction of ~87%. Shape fidelity was well retained after shrinkage across different constructs and could be stabilized by introducing secondary crosslinking. In extrusion bioprinted cell-laden constructs, myoblasts retained a considerable cell viability right after the shrinkage treatment and recovered significantly by day 1, with subsequent cell spreading and increasing proliferation over 7 days. Without the need of continued immersion in the shrinkage bath, EVER provides a hardware-independent route for refining hydrogel structures while retaining encapsulated cell compatibility.

bioengineering↗

bioRxiv2026

LiverHomo: An Integrated and Interactive Human Liver Single-Cell Atlas with Protein Interaction and Cell-Cell Communication Networks

LiverHomo is an integrated cell atlas developed from publicly available human liver single-cell RNA sequencing (scRNA-seq) datasets spanning healthy and diverse liver disease contexts. While several single-cell resources for the human liver are available, LiverHomo provides broad disease coverage and extends transcriptomic exploration through the integration of protein-protein interaction (PPI) networks and cell-cell interactions. LiverHomo provides an interactive web portal (https://liverhomo.org) for exploring cellular composition, gene expression, differentially expressed genes, Gene Ontology annotations, cell-cell interactions, and context-specific PPI networks across diseases and cell types. To facilitate intuitive access to these multidimensional data, the portal incorporates Ask LiverHomo, a natural-language assistant that interprets user queries and directs users to relevant analyses and visualizations. Interactive histograms, violin plots, network visualizations, and metadata exploration enable users to examine the atlas at cellular, transcriptomic, and protein-interaction levels, while the underlying data are readily accessible for further analysis. Together, LiverHomo provides an integrated and accessible resource for investigating cellular and molecular alterations across human liver health and disease.

bioinformatics↗

bioRxiv2026

Synaptic microRNA dysregulation orchestrates aberrant glutamatergic transmission in a human neuronal model of 22q11.2 deletion syndrome

22q11.2 Deletion Syndrome (22q11DS), the most prevalent chromosomal microdeletion disorder in humans (incidence ~1 in 4,000 live births), arises from hemizygous deletions of a 1.5-3.0 Mb region on chromosome 22. Notably, 20-30% of individuals with 22q11DS develop schizophrenia (SCZ) by early adulthood, making 22q11DS one of the strongest genetic risk factors for SCZ. However, the mechanisms by which the 22q11.2 deletion perturbs neuronal function and drive psychotic manifestations in 22q11DS remain poorly defined. In this study, we generated human 2D cortical neurons and 3D cortical organoids from induced pluripotent stem cells (iPSCs) derived from clinically well-characterized individuals with 22q11DS. Cellular and electrophysiological analyses revealed that 22q11DS neurons exhibit hyperexcitability, reduced glutamatergic synaptic transmission, and impaired homeostatic synaptic plasticity, which are pathophysiological hallmarks that may be relevant to the clinical, cognitive, and psychophysiological profiles of patients. Transcriptomic profiling of neurons and synaptosomes from 22q11DS cortical organoids uncovered dysregulated immune pathways and synaptic gene networks. Integrative mRNA-microRNA network analysis identified synergistic downregulation of hsa-miR-185-5p and hsa-miR-128-3p at synapses, driving aberrant regulation of immune and synaptic transcripts. Experimental knockdown of these microRNAs in control neurons recapitulated the molecular and functional phenotypes of 22q11DS neurons, thereby establishing a mechanistic link to synaptic dysfunction and impaired plasticity. Collectively, these findings delineate a multimodal mechanistic framework that bridges genetic vulnerability, synaptic pathology, and psychosis penetrance in 22q11DS, positioning dysregulated synaptic microRNAs as nodal regulators of neurodevelopmental networks and potential therapeutic targets.

neuroscience↗

bioRxiv2026

Multi-omics reveals accumulation mechanisms underlying differences in sesquiterpenoid content across different growth environments of Atractylodes macrocephala rhizome

This study aimed to explore mechanisms driving differential sesquiterpenoid accumulation in Atractylodes macrocephala rhizome (AMR) under different growth environments. Root and rhizosphere soil samples were collected from wild, imitated wild, one- and two-year cultivated AMR. Combined metabolomic, transcriptomic and microbiomic profiling was carried out to investigate alterations in sesquiterpenoid levels, root-associated microbiota, and terpenoid biosynthetic genes under different growth environments. Metabolomics revealed that wild AMR exhibited higher pyruvate consumption and accumulated more atractylone and atractylenolides. Transcriptomic analysis demonstrated that the genes encoding key MEP pathway enzymes (DXS, DXR, MCT, HDS) and the genes encoding the sesquiterpenoid biosynthetic enzyme GDS were significantly upregulated in wild AMR. In contrast, the genes encoding triterpenoid synthetic enzymes (SQS, SQE, {beta}-AS) were downregulated, redirecting metabolic precursors toward sesquiterpenoid synthesis. Microbial community structures differed substantially across groups. Further analysis suggested rhizosphere microorganisms were important contributors to AMR medicinal quality, and sesquiterpenoid metabolites accumulated in AMR roots, together with the rhizosphere microenvironment, jointly shape specific rhizosphere fungal assembly. This study systematically revealed the synergistic regulatory relationships among sesquiterpenoids metabolism, gene expression, growth environment, and root-associated microbes, providing multi-omics evidence for clarifying the mechanism by which these factors coordinately regulate the quality of AMR.

plant biology↗

bioRxiv2026

Patronin condensation integrates recognition, protection and organization of microtubule minus ends

Microtubule minus ends are central to non-centrosomal microtubule organization, yet how their recognition, protection and molecular organization are integrated remains unclear. Here we show that Drosophila Patronin forms dynamic condensates at microtubule minus ends through a prion-like domain (PrLD). PrLD-mediated condensation cooperates with the CKK domain and a second CKK-independent recognition region to convert weak or broadly distributed microtubule-binding activities into persistent minus-end recognition and tracking. Replacing the PrLD with a heterologous phase-separating HNRNPA1 IDR restores minus-end targeting, indicating that condensation capacity rather than PrLD primary sequence is critical. Patronin condensates further form a protective cap that resists minus-end depolymerization and recruit the cytoskeletal regulators Sas-4, Katanin and Ena. Disrupting PrLD multivalency impairs Patronin localization at multiple developmental sites and causes early organismal lethality. Thus, Patronin condensation creates a physiologically essential microtubule minus-end compartment coupling end recognition, stabilization and cytoskeletal organization.

cell biology↗

bioRxiv2026

The protein phosphatase 2A catalytic subunit Pph22 partners with Tap42 and Rrd2 to control viability and virulence in Cryptococcus neoformans

Protein phosphatase 2A regulates eukaryotic signaling, but the function of its associated regulators remains poorly understood in the human fungal pathogen Cryptococcus neoformans. Here, we used affinity purification coupled with mass spectrometry and identified 81 candidate proteins associated with the catalytic subunit Pph22, including the scaffold subunit Tpd3, the regulator Tap42, and the protein phosphatase methylesterase 1. Conditional-expression and meiotic spore analyses supported an essential role for TAP42 in viability. We identified CNAG_05505 as the Rrd2 ortholog and detected an interaction between Rrd2 and Pph22 in a yeast two-hybrid assay. Deletion of RRD2 impaired thermotolerance, altered responses to multiple stresses and antifungal agents, reduced melanin and capsule production, delayed sexual development, and inhibited titan cell formation. Mutants also displayed altered cell wall staining and reduced expression of genes involved in chitin synthesis and deacetylation. RRD2 deletion increased basal Hog1 phosphorylation, whereas PPH22 overexpression reduced it. Double-mutant analysis revealed phenotype-dependent genetic interactions between RRD2 and HOG1. Although RRD2 deletion did not significantly alter overall survival in the Drosophila infection assay, it markedly attenuated virulence in mice: all mutant-infected mice survived the 70-day observation period, and fungal burdens were reduced across multiple organs at 21 days post-infection. These findings distinguish the essential contribution of Tap42 from the broad roles of Rrd2 in stress adaptation, morphogenesis, cell surface organization, and mammalian virulence, extending the functional analysis of the cryptococcal protein phosphatase 2A regulatory network.

microbiology↗

bioRxiv2026

Beyond RMSD: Deterministic Dlow Matching for Ultrafast and Physically Validated Transition-State Generation

Transition state (TS) generation is typically evaluated by geometric similarity, yet low root-mean-square deviation (RMSD) does not establish first-order saddle-point character or reaction-path connectivity. Here we introduce Kairos-GFM, a deterministic equivariant flow-matching model that combines a two-dimensional reaction graph with the Kabsch-aligned mean of three-dimensional reactant and product geometries. Using 881 Transition1x reactions whose reference TSs passed strict saddle-point and bidirectional intrinsic reaction coordinate validation, Kairos-GFM generates one candidate in 0.0118 s with a median RMSD of 0.14 [A]. A hierarchical physical-validation framework--spanning reaction-center geometry, raw single-point energy, DFT saddle-point optimization, harmonic frequency analysis, and IRC endpoint matching reveals that low RMSD and saddle-point convergence do not guarantee the intended reaction channel. Kairos-GFM recovers the target channel in 75.94% of reactions, outperforming diffusion-based baselines but remaining below transport-based methods. These results position Kairos-GFM as a rapid initial-geometry generator for quantum-chemical refinement and provide a transferable validation standard that distinguishes geometric similarity from physical fidelity.

biochemistry↗

bioRxiv2026

From single-sequence structure prediction to protein fitness landscape through a composable, epistasis-aware mutation atlas

Mapping the multi-mutant fitness landscape is vital to protein engineering, but is challenging due to the vast combinatorial sequence space awaiting exploration. A central difficulty lies in the accurate and efficient modeling of non-additive epistatic effects among individual mutations, which partially arise from the physical inter-residue interactions prescribed by the protein structure. Existing fitness predictors usually perform well on single mutants but become less powerful for higher-order mutants, due to the lack of explicitly considering the relationship between sequence, structure and function of the target protein. Here, we present an end-to-end framework named Cerebra-Epistasis, which couples a single-sequence structure predictor that explicitly endows the structure awareness beyond the conventional sequence-fitness mapping with a downstream fitness prediction network that deliberately models the non-linear epistatic effects beyond the traditional additive terms. When evaluated across diverse assays, Cerebra-Epistasis outperforms the other state-of-the-art baselines in multi-mutant fitness prediction, with enhanced advantage over increasing mutation orders. Moreover, our special design on the epistasis modeling allows reliable extrapolation from low-order mutant data to unseen higher-order combinations, enabling one-shot inference of the overall mutation atlas from the starting sequence, a benefit that supposedly introduces three orders of magnitude acceleration in the landscape-scale prediction.

bioinformatics↗

bioRxiv2026

Extended normothermic machine perfusion preserves viability and tissue integrity of ex vivo human intestine segments

Human intestinal diseases, including inflammatory bowel disease (IBD), are difficult to model because existing animal and in vitro systems do not capture the integrated vascular, immune, and metabolic complexity of the intestine. Here, we establish a custom normothermic machine perfusion platform that maintains surgically resected human intestinal tissue for up to 72 hours under near-physiological conditions. Discarded specimens from patients with nonmalignant intestinal diseases, including IBD and diverticulitis, were continuously perfused at 37{degrees}C with real-time hemodynamic and metabolic monitoring. Perfusion preserved tissue viability, mucosal architecture, epithelial integrity, oxygen consumption, metabolic activity, and vascular patency. Daily perfusate sampling enabled longitudinal profiling and experimental modulation of inflammatory mediators, revealing patient-specific immune states. This long-duration platform bridges reductionist in vitro models and clinical disease, enabling mechanistic studies of intestinal inflammation and future testing of personalized therapies in intact patient-derived tissue.

bioengineering↗

bioRxiv2026

MutCleaner: Cleaning and Standardizing Biological Mutation Datasets for Variant Effect Prediction

Summary: Protein mutation datasets are widely used in variant effect prediction and protein engineering, but datasets from different sources often lack consistent conventions for mutation representation, sequence representation, data organization, and experimental labels, making these resources difficult to integrate directly and limiting their use in downstream analyses and modeling. MutCleaner is an extensible Python framework that cleans, validates, and standardizes protein- and codon-level mutation datasets through composable cleaning pipelines, unified sequence and mutation data structures, and dataset-specific cleaners. It provides standardized resources covering 16 protein and codon mutation datasets with more than 12.14 million mutation records. Availability and implementation: MutCleaner is an open-source Python package released under the Apache License 2.0. The source code is available on https://github.com/xulab-research/MutCleaner, the package is distributed through https://pypi.org/project/mutcleaner/, and the documentation is available https://xulab-research.github.io/MutCleaner/.

bioinformatics↗

bioRxiv2026

Avs2 drives non-canonical tetrameric assembly of trypsin-like domain for anti-phage defense

Bacteria have evolved diverse anti-phage defense systems, with the antiviral STAND family (Avs) representing one of the most diverse and widespread, encompassing at least 90 distinct families, yet only Avs3, Avs4, Avs5 and Avs7 have been well characterized. Here, we elucidated the molecular mechanism of Avs2-trypsin-MBL system, where phage terminase recognition by Avs2 triggers coupled activation of the protease and nuclease activities of trypsin-MBL. Cryo-EM structure of Avs2-trypsin-terminase and biochemical analysis reveal that the binding of terminase ATPase domain triggers the assembly of Avs2 into tetramer, with two unique ATP molecules bridging ATPase active-site recognition by TPR domain. This tetramerization drives the fused trypsin into an active C4-symmetric assembly, an architecture distinct from the conventional non-defense trypsin. Our study unravels the activation mechanism of Avs2-trypsin-MBL system, expanding our understanding on commonality and diversity of widespread Avs-mediated anti-phage immunity, alongside the structural and functional adaption of trypsin.

microbiology↗

bioRxiv2026

Modeling Risk Group 4 virus infection and antiviral treatment in microfluidic lung organ-on-chips in maximum containment laboratories

Development of candidate countermeasures against human pathogens frequently includes nonhuman animal experimentation. Preclinical animal pathogen exposure studies are conducted to model diseases and accumulate preliminary and hypothetically translatable data to inform and justify the design of clinical trial evaluation of countermeasure safety and efficacy. In addition to frequent ethical critiques, challenges associated with animal experimentation include considerable resources needed to achieve statistical power and robustness, replicability and reproducibility concerns, potentially compromised objectivity through lack of blinding, fundamental species-specific biological differences, and risk of unpredictable pathogen adaptation to the experimental animal. Recent U.S. and U.K. government initiatives aim to reduce animal experimentation by complementing or potentially replacing them with new approach methodologies (NAMs), i.e., increasingly sophisticated in silico, in chemico, and in vitro approaches. We piloted development of one type of NAM, organ-on-chips (OOCs), in the highly challenging environment of a maximum (biosafety level 4) containment laboratory. Using a Risk Group 4 virus, Nipah virus (NiV), and two types of lung OOCs seeded with human or porcine cells, we demonstrated the recapitulation of key features of NiV lung infection, including viral infection, replication, and translocation, that are associated with proinflammatory cytokine secretion, immune cell recruitment, and disruption of the air-liquid interface barrier. We reproduced the known anti-NiV activity of remdesivir and evaluated that of another potential antiviral, zotatifin. Our results pave the way for similar applications of advanced microphysiological systems for modeling infections caused by high-consequence viruses.

microbiology↗

bioRxiv2026

The HES1-SOD1 Antagonism Shapes Senescence Heterogeneity and Impacts Metastatic Relapse of Circulating Tumor Cells

Circulating tumor cells (CTCs) encounter multiple challenges within the blood microenvironment, including oxidative stress, flow shear forces, and immune surveillance, often leading to anoikis. Recently, a transitional state of CTC senescence has been identified, contributing to metastatic inefficiency. However, the molecular mechanisms linking senescent CTCs to disease relapse remain to be defined. By integrating a genetic model of cortactin knockdown-induced CTC senescence with single-cell multi-omic analyses, we revealed two distinct senescent CTC subpopulations marked by HES1 expression levels. These HES1low and HES1high subpopulations exhibited differential evolutionary trajectory dynamics and unique molecular and metabolic signatures, which were significantly correlated with adverse clinical outcome across several patient cohorts. HES1low senescent CTCs displayed enhanced mitochondrial fitness, oxidative phosphorylation, and ROS-detoxifying capabilities, resulting in more efficient tumor regrowth with a pro-inflammatory and thrombotic phenotype when compared to the HES1high group. Mechanistically, HES1 directly bound to the Sod1 promoter and repressed its expression, leading to redox imbalance and mitochondrial dysfunction that were linked to weakened tumor regrowth capacity. Both senescent CTC subpopulations were broadly resistant to cytotoxic and targeted therapies, yet they showed elevated dependency on anti-apoptosis programs that make them susceptible to dual blockade by SOD1 inhibitor and the anti-senolytic drug ABT737 in vivo. Finally, in a prospective cohort of on-treatment melanoma patients, HES1 senescent CTCs were highly enriched in patients with progressive disease. Thus, the HES1-SOD1 antagonism shapes CTC senescence heterogeneity and contributes to differential tumor relapse, which can be therapeutically explored for eliminating residual metastatic disease.

cancer biology↗

bioRxiv2026

Phagocytic activity of perivascular cell promotes CNS injury pathology

Injury, stroke, and neurological diseases cause persistent accumulation of cellular debris that deteriorates lesion microenvironment and impedes central nervous system (CNS) repair. Debris clearance in the injured CNS has long been attributed primarily to microglia and infiltrating macrophages. Here, we identify perivascular cells as previously unrecognized phagocytes that expand after injury and exhibit robust phagocytic activity. Perivascular cell phagocytosis is conserved across multiple mouse models of CNS injury and human stroke lesions. These cells exhibit key hallmarks of phagocytosis, including LC3-associated phagocytosis for efficient lysosomal degradation. Mechanistically, phosphatidylserine serves as the eat-me signal and Axl mediates myelin debris uptake. Myelin phagocytosis drives perivascular cell proliferation, fibrosis and lesion progression. Genetic deletion of Axl in perivascular cells or pharmacological inhibition with the FDA-approved Axl inhibitor Gilteritinib reduces pathology and improves functional recovery after spinal cord injury. Together, these findings establish Axl-dependent perivascular cell phagocytosis as a therapeutic target for CNS repair.

neuroscience↗

bioRxiv2026

Brassinosteroid-auxin crosstalk shapes rice flag leaf angle to boost dense planting yield

Flag leaf angle (FLA) critically determines rice yield potential under dense planting conditions. As two pivotal phytohormones determine rice FLA, the antagonistic interaction between brassinosteroid (BR) and auxin remains largely uncharacterized. We here demonstrate that BR signaling reduces auxin biosynthesis to control FLA via regulating the biosynthesis of secondary cell wall (SCW). Genetic evidence demonstrates OsYUC8 mutants disrupt SCW formation, leading to increased FLA. At the molecular level, the BR-related transcription factor OsBZR1 directly binds to and represses OsYUC8 promoter activity, thereby fine-tuning auxin-mediated SCW biosynthesis. Field evaluations reveal that osbzr1 mutants display optimized flag leaf architecture and improved yield performance under high-density cultivation. Our study not only delineates the antagonistic BR-auxin interaction governing FLA but also establishes a genetic strategy for manipulating crop architecture to maximize yield in dense planting conditions. One-sentence summaryOsBZR1-mediated repression of OsYUC8-driven auxin biosynthesis modulates secondary cell wall formation to optimize flag leaf architecture, providing a genetic strategy for maximizing yield under high-density cultivation.

plant biology↗

bioRxiv2026

GAMETE maps the genetic architecture of chromatin accessibility in rice pollen at single-nucleus resolution

BackgroundDissecting the genetic basis of cell-type-specific gene regulation during gametogenesis remains a major challenge. Population-level studies mask cellular heterogeneity, while the extreme data sparsity of single-cell profiling has precluded robust genetic mapping. ResultsWe present GAMETE (Genetic Architecture Mapping of Epigenetic Traits at single-nucleus resolution), an integrated framework combining MPS-ATAC-seq, a high-throughput single-nucleus ATAC-seq method, with robust computational approaches for genotype inference and genetic mapping from sparse single-nucleus data. Applying GAMETE to hybrid rice pollen, we simultaneously profiled chromatin accessibility and inferred the genotypes of 4,887 individual haploid nuclei, revealing distinct chromatin landscapes across pollen cell types. This uncovered an unexpected elevation of chromatin accessibility at gypsy retrotransposons in microspores preceding their silencing in sperm cells, exposing a surveillance gap that may contribute to genome expansion. The synchronized profiling enabled us to construct a single-cell recombination map, map segregation distortion loci and trace their developmental origins, and identify 16,113 chromatin accessibility QTLs (caQTLs), 48.6% of which exhibited pronounced cell-type specificity. Analysis of introgression lines supported a cell-type-specific trans-acting caQTL regulating the pollen-essential gene DTM1. ConclusionsThis work establishes GAMETE as a broadly applicable framework for dissecting the genetic architecture of chromatin accessibility during gametogenesis without the need for subsequent generations.

genomics↗