Biology subjects

Si, H.

Publications and source records attributed to Si, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Functional and evolutionary insights into the emerging tet(X4)-carrying non-O1/O139 Vibrio cholerae from retail pork

The tigecycline resistance gene tet(X4) is prevalent in Enterobacteriaceae, particularly in Escherichia coli. To our knowledge, no study has reported the dissemination dynamics of tet(X4) in Vibrio spp. Herein, we isolated and characterized a first tet(X4)-positive non-O1/O139 Vibrio cholerae isolate from retail pork. Genomic sequencing identified a novel tet(X4) variant in the V. cholerae chromosome, harboring a G568A nucleotide substitution that resulted in an Ala190Thr (A190T) amino acid substitution in Tet(X4). While this Tet(X4)-A190T variant conferred lower phenotypic resistance to tetracyclines (including tigecycline) than the wild-type Tet(X4), its overall catalytic efficiency against these antibiotics was paradoxically enhanced despite a reduced substrate affinity. Genomic comparisons revealed that two copies of ISCR2 flanked the variant gene, and the structure was ISCR2-hp-hp-abh-tet(X4)G568A -ISCR2, which is highly homologous to the reported E. coli plasmids carrying tet(X4). In addition, it confirmed the presence of an ISCR2-mediated circular intermediate, proving this modules capacity for horizontal transfer of the tet(X4)G568A variant. Furthermore, the ISCR2-tet(X4) genetic structure carrying the G568A substitution was integrated within a chimeric SXT/R391-like integrative and conjugative element (ICE), which is also serving as a vehicle for genetic dissemination. As per our knowledge, this is the first report on the emergence of SXT/R391-like ICE carrying tet(X4) in Vibrio strains. Our finding demonstrates that the clinically relevant tigecycline resistance gene tet(X4), previously confined mainly to Enterobacterales from humans and livestock, is now actively spreading into environmental Vibrio populations. This cross-species transfer highlights a previously underappreciated ecological and public health concern in aquatic ecosystems.

microbiology↗

bioRxiv2026

Phyllosphere and rhizosphere microbiomes empower Nicotiana tobacum complex traits dissection and prediction

Understanding how plant-associated microbiomes interact with host genome variation to influence agronomic traits is essential for advancing microbiomeassisted crop improvement. In this study, we characterized the phyllosphere and rhizosphere microbiomes of 164 diverse Nicotiana tabacum accessions using 16S rRNA sequencing and integrated these data with host genomic variation and 22 agronomic traits. The two microbiomes exhibited distinct taxonomic structures, diversity patterns, and predicted metabolic functions. Microbiome genomewide association studies identified extensive host genetic control over microbial abundance, including 49 shared genomic loci that explained nearly half of the heritable variation in both microbiomes. Microbiomewide association studies revealed biologically meaningful associations between specific ASVs and agronomic traits. However, network analysis demonstrated that microbial subcommunities, rather than individual taxa, contributed substantially to phenotypic variation. Then, colocalization analysis further identified genetic variants jointly influencing microbial abundance and metabolite traits, highlighting potential host-microbe-trait causal links. Incorporating microbiome data into genomic selection models, we successfully improved prediction accuracy for several traits, especially plant architecture and flowering. Together, this work provides a comprehensive populationlevel framework linking host genetics, microbiome composition, and agronomic traits in tobacco, offering new insights for microbiomeinformed breeding strategies.

plant biology↗

bioRxiv2025

Comparative Analysis of Pathology Foundation Models for Automated Detection of Tertiary Lymphoid Structures in H&E-Stained Digital Pathology Images

Tertiary lymphoid structures (TLS) have been observed in solid tumors and have been associated with better outcomes in patients treated with immunotherapy, but their dynamic nature makes identifying TLS in clinical samples challenging. Recently, pathology foundation models have emerged as powerful tools in computational pathology. In this study, we aimed to develop a computational tool capable of identifying TLS across different cancer types. To this end, we utilized multiple pathology foundation models, along with the ImageNet-pretrained ResNet50 as a baseline, to identify TLS in pancreatic ductal adenocarcinoma (PDAC) and head and neck squamous cell carcinoma (HNSCC) using hematoxylin and eosin (H&E) stained images from The Cancer Genome Atlas (TCGA) and a licensed Real-World Evidence (RWE) cohort. Both pathologist-annotated and transcriptomic signature-based TLS outcomes were employed for performance assessment. Pathologist-identified TLS-positive tumors showed higher expression of TLS signatures in both diseases. Among the models tested, PLIP and CTransPath exhibited strong performance in identifying TLS within PDAC samples (AUC = 0.94 and 0.89, respectively). However, all models struggled in the analysis of HNSCC, likely due to the increased heterogeneity of the tumor microenvironment (TME). Despite their overall utility in detecting TLS in PDAC, all foundation models demonstrated poor performance in predicting transcriptomic signature-based outcomes in both PDAC and HNSCC. This suggests that TLS signatures may reflect broader or more transient aspects of TLS biology, whereas pathology-based assessment anchors on visible morphological features, more closely aligned with the focus of foundation model training. These findings highlight the potential of advanced pathology foundation models for TLS detection and broader tumor immune profiling tasks. These models can also be utilized on routinely collected patient biosamples with nominal costs. However, further refinement is needed to enhance their utility in tumors with more complex TME. Additionally, the identification of transcriptomics-based biomarkers from H&E images remains a significant challenge, despite advancements in digital pathology.

bioinformatics↗

bioRxiv2025

Association of haplotypes of AAP family amino acid transporters with nitrogen response and nitrogen use efficiency in rice grown under hydroponics and field conditions

The low nitrogen use efficiency (NUE) of staple food crops like rice has both economic and environmental impact. Amino acids taken up from soil or synthesized in source tissues and transported to sink tissues influence plant development and NUE. Amino acid permeases (AAPs) mediate amino acid uptake and transport and influence plant development, yield and NUE. NUE is a complex trait critical for improving rice productivity under variable N supply. Amino acid permeases such as OsAAP3, OsAAP5, and OsAAP11 have been shown to function as negative regulators of NUE in Japonica rice, yet their roles in Indica rice remain to be fully elucidated. In this study, we evaluated selected Indica genotypes under contrasting N regimes--seedlings were tested under high nitrate (HN), high ammonium (HA), and low N (LN) conditions, and field performance was assessed under N120 (optimum N) and N0 (low N). Our aim was to relate performance differences to the SNP status in these three genes, thereby clarifying their influence on N uptake, assimilation, yield potential, and N stress adaptation. ARC 10799 had non-synonymous SNP in OsAAP3, OsAAP5 and OsAAP11. Rice accessions like "Local," "NCS901," and "Bhainsa Mundariya," showed superior biomass accumulation relative to MTU1010. Interestingly, the trend observed in the NUE calculated in seedling stage was similar to those proven in field evaluation and this proves that in general, genotypes with non-synonymous mutation in AAP3, AAP5 and AAP11 in comparison to Japonica showed better growth and N content. Data suggests an N induced regulation of physiological parameters and the changes in NUE parameters was at least in part, related to variation in biomass, plant height, photosynthesis and pigment content related parameters. The comparatively dissimilar trends in shown by different AAP haplotypes indicates the possibility of high or low correlation trait-wise, offering an opportunity to identify significant contrasts in a divergent set of AAP haplotypes. The previous reports and current findings opens new avenues and insights for improving rice yield, quality and NUE by changes in AAP haplotypes that occur naturally or created by precise genome editing.

plant biology↗

bioRxiv2025

Mechanistically explainable AI model for predicting synergistic cancer therapy combinations

This study introduces a Large Language Model (LLM)-based framework that combines drug combination data with a knowledge graph to predict synergistic oncology drug combinations with mechanistic insights. Using a retrieval-augmented generation (RAG) approach, over 50,000 in vitro drug pair assay results and 1,631 human clinical trial or preclinical test entries were integrated to enhance predictive accuracy and explainability. Validation achieved an F1 score of 0.80, demonstrating the frameworks potential to streamline drug discovery and improve translational strategies in cancer treatment.

cancer biology↗

bioRxiv2025

Noncanonical Wnt/Ror2 Signaling Regulates Basal Cell Fidelity and Branching Morphogenesis in the Mammary Gland

The mammary gland epithelium relies on a delicate balance between basal and luminal cell lineages to maintain tissue homeostasis and enable proper development. While the role of canonical Wnt signaling in mammary biology is well-established, the contribution of noncanonical Wnt signaling to lineage identity has remained unclear. Noncanonical Wnt pathways are primarily associated with morphogenesis, cytoskeletal regulation, and cell migration, but whether they are required for maintaining epithelial cell fate remains largely unexplored. Here, we demonstrate that the noncanonical Wnt receptor Ror2 is expressed in both basal and luminal lineages, yet selectively maintained in basal cells throughout development, suggesting a lineage-specific function. Using a p63CreERT2/+ lineage-specific mouse model, we show that Ror2 deletion in basal epithelial cells enhances secondary and tertiary branching while driving a basal-to-luminal fate transition, marked by downregulation of basal markers (K14, K5) and upregulation of luminal markers (K8, K18, ER). Mechanistically, Ror2 loss disrupts RhoA-ROCK1-YAP1 signaling, leading to cytoskeletal reorganization, chromatin remodeling, and increased accessibility at luminal regulatory loci. Notably, ROCK1 inhibition phenocopies Ror2 loss, reinforcing the critical role of the RhoA-ROCK1 axis in basal cell maintenance. These findings provide direct genetic and mechanistic evidence that noncanonical Wnt signaling is essential for maintaining basal lineage fidelity, offering new insights into the mechanisms regulating epithelial plasticity. Given the fundamental importance of lineage stability in epithelial homeostasis, our results suggest that disruptions in Wnt/Ror2 signaling may contribute to aberrant fate transitions relevant to breast cancer progression.

developmental biology↗

bioRxiv2024

Feathered Icons: Drivers of Global Attention on Bird Species

Greater public support to conservation is needed to help address the global biodiversity crisis. However, human attention towards biodiversity is taxonomically biased, leaving many species neglected and their conservation needs unmet. Here we investigated the drivers of public and scientific interest for 10,509 bird species, measured by Wikipedia pageviews and articles in Web of Knowledge. We then used a quasi-experimental design to test the effect on public interest of published updates to the International Union for the Conservation of Nature (IUCN) Red List of threatened species (N = 479). Public and scientific interest were strongly predicted by species charisma, familiarity, utilization, and Red List category. While threatened species received significantly more attention, IUCN Red List category revisions produced asymmetric public response: uplistings (to categories of higher extinction risk) generated a significant but modest immediate increase in pageviews, while downlistings (to categories of lower risk) showed no detectable effect. The traits that predicted responsiveness, genuineness of change (real biological shifts rather than improved knowledge or revised taxonomy) and increasing population trend, differed from those driving underlying interest. These findings underscore the need to raise the profile of species lacking the charismatic or familiar traits that typically attract public and scientific interest.

ecology↗

bioRxiv2024

Deep-learning-enabled generative prevalent mutation prediction through host-to-herd in silico virus evolution

Predicting the mutation prevalence trends of emerging viruses in the real world is an efficient means to update vaccines or drugs in advance. It is crucial to develop a computational method for the prediction of real-world prevalent SARS-CoV-2 mutations considering the impact of multiple selective pressures within and between hosts. Here, a deep-learning generative framework for real-world prevalent SARS-CoV-2 mutation prediction, named ViralForesight, is developed on top of protein language models and in silico virus evolution. Through the paradigm of host-to-herd in silico virus evolution, ViralForesight reproduced previous real-world prevalent SARS-CoV-2 mutations for multiple lineages with superior performance. More importantly, ViralForesight correctly predicted the future prevalent mutations that dominate the COVID-19 pandemic in the real world more than half a year in advance with in vitro experimental validation. Overall, ViralForesight demonstrates a proactive approach to the prevention of emerging viral infections, accelerating the process of discovering future prevalent mutations with the power of generative deep learning.

evolutionary biology↗

bioRxiv2024

Natural genetic and transcriptomic variation in photosynthesis associated pathways contribute to adaptive traits variation in worldwide Arabidopsis thaliana population

Photosynthesis is the most important reaction underlying carbon fixation. Despite its potential in boosting carbon assimilation, nature variations underlying genes in photosynthesis pathway and their role in adaptive traits variation remains elusive. In this study, we investigated the genetic, transcriptomic variation of 1103 genes in photosynthesis associated pathways, including 82 photosynthesis core genes, 24 plastid-encoded RNA polymerase related genes, 2 nucleus-encoded RNA polymerase-related genes, 34 photomorphogenesis-related genes, 40 genes involved in transcription and translation (TAC) and 938 other nuclear-encoded chloroplast-targeted genes. By de novo assembling the chloroplast genomes of 28 representative accessions and leveraging whole-genome, transcriptome sequencing data from the 1001 Genome Project, we revealed extensive natural genetic and transcriptome variations these genes in worldwide Arabidopsis thaliana population. 34.0% of them were identified with regulatory variations in expression quantitative locus mapping (eQTL) mapping, including key components of Rubisco (RBCS1B, RBCS2B), and Rubisco activase (RCA). Genome-wide and transcriptome-wide association analysis (GWAS/TWAS) showed that these genetic and transcriptomic variations made considerable contribution to variation of adaptive traits. Overall, our study provides insight into the natural genetic variation of these genes among worldwide Arabidopsis thaliana accessions and their role in complex traits variation and adaptation.

plant biology↗

bioRxiv2024

High Frequency Terahertz Stimulation Alleviates Neuropathic Pain by Inhibiting the Pyramidal Neuron Activity in the Anterior Cingulate Cortex of mice

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7-10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximate 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex through enhancing the voltage-gated K+ and also the leak K+ conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising application in other nervous system diseases.

neuroscience↗

bioRxiv2023

Evolution-guided large language model is a predictor of virus mutation trends

The increasing frequency of emerging viral infections necessitates a rapid human response, highlighting the cost-effectiveness of computational methods. However, existing computational approaches are limited by their input forms or incomplete functionalities, preventing a unified prediction of diverse viral variation drivers and hindering in-depth applications. To address this issue, we propose a unified evolution-driven framework for predicting virus variation drivers, named E2VD, which is guided by virus evolutionary traits priors. With evolution-inspired design, E2VD comprehensively and significantly outperforms state-of-the-art methods across various virus variation drivers prediction tasks. Moreover, E2VD effectively captures the fundamental patterns of virus evolution. It not only distinguishes different types of mutations but also accurately identifies rare beneficial mutations that are critical for virus to survival, while maintains generalization capabilities on different viral lineages. Importantly, with predicted biological drivers, E2VD perceives virus evolutionary trends, in which potential high-risk mutation sites are accurately recommended. Overall, E2VD represents a unified, structure-free, and interpretable approach for analyzing and predicting viral evolutionary fitness, providing an ideal alternative to costly wet-lab measurements to accelerate responses to emerging viral infections.

bioinformatics↗

bioRxiv2023

Comprehensive analyses of 1771 transcriptome from seven tissues enhance genetic and biological interpretations of maize complex traits

By analyzing 1771 RNA-seq datasets from seven tissues in a maize diversity panel, we explored the landscape of multi-tissue transcriptome variation and evolution patterns of tissue-specific genes, and built a comprehensive multi-tissue gene regulation atlas to understand the genetic regulation of maize complex trait. Using transcriptome-wide association analysis, we linked tissue-specific expression variation of 45 genes to variation of 11 agronomic traits. Through integrative analyses of tissue-specific gene regulatory variation with genome-wide association studies, we detected relevant tissue types and candidate genes for a number of agronomic traits, including leaf during the day for anthesis-silking interval (GRMZM2G093210), leaf during the day for kernel Zeinoxanthin level (GRMZM2G143202), and root for ear height (GRMZM2G700665), highlighting the contribution from tissue-specific gene expression to variation of agronomic trait. Our findings provide novel insights into the genetic and biological mechanisms underlying complex traits in maize, and the multi-tissue regulatory atlas serves as a primary source for biological interpretation, functional validation, and genomic improvement of maize.

genetics↗

bioRxiv2023

Polygenic basis of strong and rapid flowering time response to environment perturbations in wild Arabidopsis thaliana population

Despite the importance in understanding the impact of climate change, the genetics of rapid response to changing environments and its role in adaptive evolution remains elusive. Here, we studied flowering time response to environment changes using 514 Arabidopsis thaliana worldwide accessions with re-sequencing genomes and flowering time measurements from ten unique environments with variable temperature, drought, daylight and competition stresses. We revealed a polygenic basis of flowering time mean and plasticity, underpinned by 52 mean and plasticity QTL. Widespread interaction between mean QTL, polygenic background and surrounding environments considerably altered the amount of additive genetic variance and allelic effects of detected QTL. This caused variability in phenotype plasticity and across environment variation in genetic variance, resulting in rapid flowering time response to environment perturbations. In addition, the plastic alleles showed a higher correlation with the environment factors than that from randomly sampled alleles, suggesting a potential role in climate adaptation. We therefore proposed a polygenic interaction model, whereby large effect QTL and polygenic background simultaneously interacted with the surrounding environment, underlying rapid response to changing environments. Results from our study thus provided deeper insights into the genetics of plasticity, with potential benefit in genomic selection of crops in heterogeneous environments and predicting changes in species distribution and the evolutionary trajectory of wild populations.

genetics↗

bioRxiv2023

Analysis of the heterogeneity and complexity of murine extraorbital lacrimal gland via single-cell RNA sequencing

PurposeThe lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting the aqueous layer of the tear film. However, a healthy lacrimal glands inventory of cell types and heterogeneity remains understudied. MethodsHere, 10X genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 48,077 high-quality cells, an atlas of cell heterogeneity was produced, and cell types were defined by classic marker genes. The possible functions of these cells and the pseudotime trajectories for certain cell populations were analyzed through bioinformatics. In addition, a preliminary analysis of the cell-cell communication network in ELG was performed. ResultsOver 41 subclasses of cells were identified, including 9 kinds of glandular epithelial cells, 7 kinds of fibroblasts, 10 kinds of myeloid-derived immune cells, at least 10 kinds of lymphoid-derived immune cells, 3 kinds of vascular-associated cell subsets, and 2 kinds of Schwann cells. Analysis of cell-cell communication networks revealed that innate lymphoid cells were closely associated with other cells. ConclusionsThis study provides the first comprehensive transcriptome atlas and related database of mouse ELG. This resource can aid in a deeper understanding of lacrimal gland biology and pathophysiology of its related diseases.

bioinformatics↗

bioRxiv2023

GenBank genomics highlight the genomic features, genetic diversity and regulation of morphological, metabolic and disease-resistance traits in Nicotiana tabacum

Nicotiana tabacum is a model organism in plant molecular and pathogenic research and has significant potential in the production of biofuels and active pharmaceutical compounds in synthetic biology. Because of the large allotetraploid genome of tobacco, its genomic features, genetic diversity and genetic regulation of many complex traits remain unknown. In this study, we present a nearly complete chromosome-scale assembly of N. tabacum and provide evidence that homoeologous exchange between subgenomes and epigenetic remodelling are likely mechanisms of genome stabilization and subgenome coordination following polyploidization. By leveraging GenBank-scale sequencing and phenotyping data from 5196 lines, geography at the continent scale, rather than types assigned on the basis of curing crop practices, was found to be the most important correlate of genetic structure. Using 178 marker{square}trait associations detected in genome-wide association analysis, a reference genotype-to-phenotype map was built for 39 morphological, developmental, and disease-resistance traits. A novel gene, auxin response factor 9 (Arf9), associated with wider leaves after being knocked out, was fine-mapped to a single nucleotide polymorphism (SNP). This point mutation alters the translated amino acid from Ala203 to Pro203, likely preventing homodimer formation during DNA binding. Our analysis also revealed signatures of positive and polygenic selection for multiple traits during the process of selective breeding. Overall, this study demonstrated the power of leveraging GenBank genomics to gain insights into the genomic features, genetic diversity, and regulation of complex traits in N. tabacum, laying a foundation for future research on plant functional genomics, crop breeding, and the production of biopharmaceuticals and biofuels.

genetics↗

bioRxiv2021

QSAR Model Based Gradient Boosting Regression of N-Arylsulfonyl-Indole-2-Carboxamide Derivatives as Inhibitors for Fructose-1,6-Bisphosphatase

As is known to all, diabetes metellius is a global health threaten and it has caused worldwide attention of scientists. To get a better investigation of the drug design of diabetes, we used heuristic method to established the linear model and used Gradient Boosting Regression to establish the nonlinear model of Fructose-1,6-Bisphosphatse inhibitor successively. In this study, 84 derivatives of N-Arylsulfonyl-Indole-2-Carboxamide were introduced into the models, two outstanding QSAR models with 2 molecule descriptors were established successfully. Grandient Boosting Regression rendered a good correlation with R2 of 0.943 and MSE of 0.135 for the training set, 0.916 and 0.213 for test set, which also proves the feasibility of the implementation of the new method GBR in the field of QSAR. Meanwhile, the optimal model displayed wonderful statistical significance. This study shows unlimited potential for design of new drugs for diabetes.

biochemistry↗

bioRxiv2021

Non-canonical Wnt/Ror2 signaling status regulates cell-matrix crosstalk to prompt directional tumor cell invasion and dissemination in breast cancer

Bidirectional cell-extracellular matrix (ECM) interactions represent fundamental exchanges during tumor progression. We demonstrate the noncanonical Wnt receptor, Ror2, regulates tumor cell-driven matrix remodeling in models of breast cancer. Wnt/Ror2 loss-of-function triggers tumor cell invasion, accompanied by changes in actin cytoskeleton, adhesion, and collagen crosslinking gene expression programs. E-cadherin levels decline upon Ror2 depletion, and spatially, we pinpoint the upregulation and redistribution of 5 and {beta}3 integrins together with the production of fibronectin in areas of invasion. Wnt/{beta}-catenin-dependent and Wnt/Ror2 alternative Wnt signaling appear to regulate distinct functions for tumor cells regarding their ability to modify cell-ECM exchanges during invasion. Furthermore, blocking either integrin or focal adhesion kinase (FAK), a downstream mediator of integrin-mediated signal transduction, abrogates the enhanced migration observed upon Ror2 loss. These results reveal a critical function for the alternative Wnt receptor, Ror2, as a determinant of reciprocal communication between tumor cells and ECM during cancer invasion and metastasis.

cancer biology↗

bioRxiv2021

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans

Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1{Delta}/{Delta} pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase (A) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of the cAMP pathway is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis. AUTHOR SUMMARYThe human fungal pathogen Candida albicans switches between budding and filamentous hyphal morphologies to gain advantages for virulence and survival in the host. Although adenylyl cyclase has been thought to be a master regulator that controls this switch, we identified C. albicans pseudorevertant mutants that grow better and form hyphae in the absence of adenylyl cyclase and cAMP. The mutant cells were also able to induce hyphal-associated genes in the absence of cAMP that are needed for virulence. Integrating information from different omics approaches identified cAMP-independent mechanisms that promote hyphal growth. This includes phosphoproteomic studies that revealed key roles for the Cdc28 cyclin-dependent kinase and casein kinase 1 in promoting hyphal growth. In addition, integrating transcriptomic and proteomic data revealed that post-transcriptional mechanisms regulate the levels of a set of key transcription factors that are important for hyphal induction, suggesting a novel form of translational regulation. These studies better define the pathways that stimulate C. albicans to switch from budding to hyphal growth, which is important for invasion into tissues, escape from the immune system, and biofilm formation.

microbiology↗