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Tsuda, K.

Publications and source records attributed to Tsuda, K..

At least 19 recordsLinked to original sources

pLM-bVAE: protein language model-enhanced binary representation improves quantum annealing-based protein sequence design

Quantum annealing (QA) has been explored as an approach for protein design in vast combinatorial sequence spaces. Applying QA to protein sequence design requires amino acid sequences to be encoded as binary vectors, and optimized vectors to be decoded back into amino acid sequences. Thus, both the quality of binary encoding and sequence reconstruction accuracy are important for effective QA-based optimization. Binary variational autoencoder (bVAE) has been used to map protein sequences to binary representations in QA-based protein sequence design. However, bVAE was originally developed for natural language modeling, and its suitability for proteins has not been systematically evaluated. Here, we present pLM-bVAE, which incorporates protein representations derived from a pretrained protein language model (pLM) into the original bVAE model. In computational experiments on three public protein variant datasets, pLM-bVAE showed higher sequence reconstruction accuracy and binary encoding performance than bVAE. Moreover, we incorporated pLM-bVAE into a QA-based protein sequence design framework. Across all three datasets, pLM-bVAE generated more high-scoring sequences with greater sequence dissimilarity from the training and validation data than bVAE. Our results demonstrate that pLM-bVAE provides an effective binary representation for improving QA-based protein sequence design. Availability The source code used in this manuscript is available at https://github.com/hueda8/pLM-bVAE.

bioinformatics↗

Integrative analysis of the MDM2 promoter switch and cellular lineage plasticity in colorectal cancer: a contrast between the autonomous-proliferation type (CIN/CMS2) and the environment-adaptive type (MSI/gastric metaplasia)

Background: Biomarkers that stratify colorectal cancer (CRC) by therapeutic responsiveness and are measurable directly in biopsy specimens remain insufficiently established. We investigated whether usage of the dual MDM2 promoters (P1/P2) acts as a molecular switch separating two diametrically opposed CRC phenotypes: a chromosomal instability type and an environment adaptive type (microsatellite instability/serrated pathway with gastric metaplasia). Methods: Sixty three organoid samples from 22 patients with CRC were classified morphologically by deep learning (VGG16) and molecularly by an MDM2 Splicing Index derived from expression arrays. The P1 and P2 signatures (gene sets characterizing P1 and P2dominant samples) were externally validated in TCGA-COAD/READ (n = 624) and GSE39582 (n = 536), 1,160 cases in total, and therapeutic implications were tested in public cell line panels (GDSC2, DepMap) and in 65 lines of an independent patient derived CRC organoid biobank. Results: Deep learning morphological classification reached 98.5% test accuracy (64/65), and morphology corresponded to P1/P2 isoform usage: Type1 (compact glandular) morphology predominated in P1 dominant samples (median Type1 fraction 0.826 versus 0.444) and non Type1 (cystic mucinous) morphology in P2 dominant samples (AUC 0.79). Both signatures differed across the four consensus molecular subtypes , and the P2 signature was higher in mismatch repair deficient (microsatellite-unstable) tumors. Promoter usage quantified directly (P2_index) was higher in TP53 wild type tumors , consistent with P2 being p53-inducible. TP53 wild type cell lines were more sensitive to the MDM2 inhibitor Nutlin 3a and were more dependent on MDM2 in the DepMap CRISPR screen ; among 198 GDSC2 drugs, Nutlin 3a correlated most strongly with the P2 score. In the independent biobank, TP53 wild type lines (17) were more sensitive to nutlin-3 than mutant lines (48) (median log(IC50) 1.386 versus 4.283). Conclusions: MDM2 promoter choice (P1/P2) co-varies with the lineage identity of cancer cells and with the secretory, mucin rich character of the tumor tissue, consistent with a molecular-switch role alongside p53 suppression. The MDM2 P1/P2 ratio, measurable by RT qPCR or targeted NGS, is a candidate molecular-classification and therapeutic-stratification biomarker corresponding robustly to CMS, MSI, and TP53 mutation status.

bioinformatics↗

Knowledge-guided Bayesian optimization using pre-trained LLMs speeds up the identification of superior genotypes from germplasm collection

BackgroundGermplasm collections contain wide genetic diversity that is valuable for plant breeding, but conducting phenotypic evaluation for all genotypes in field trials is rarely feasible. Bayesian optimization offers a way to decide, season by season, which genotypes to cultivate in order to identify superior genotypes with fewer evaluations. However, standard Bayesian optimization commonly starts from randomly selected genotypes and mainly relies on surrogate models built from marker genotype information, while the text-based passport information that accompanies germplasm is not fully used. We examined whether pre-trained large language models can provide prior knowledge that improves these decisions in germplasm evaluation. ResultsWe constructed a large-language-model-guided Bayesian optimization framework that introduces large language models into two parts of the Bayesian optimization workflow. In zero-shot warmstarting, a large language model proposes initial genotypes using passport information such as cultivar name, country of origin, and subpopulation, optionally together with principal component scores derived from genome-wide single-nucleotide-polymorphism markers. In addition, we evaluated a large-language-model-based surrogate model that predicts phenotypic values for untested genotypes using in-context learning from previously evaluated genotypes. Using a rice germplasm panel and two target traits (seed number per panicle for maximization and protein content for minimization), we compared strategies. For seed number per panicle, zero-shot warmstarting with a general-purpose instruction-following model reduced the number of evaluated genotypes needed to reach the best genotype, whereas improvements were small for protein content. When genomic information was available, Gaussianprocess-based Bayesian optimization was the strongest overall approach, while the large-language-model-based surrogate model outperformed random baselines and was competitive in some settings. When genomic information was not available, predictions based on passport information improved efficiency compared with fully random strategies. ConclusionsPre-trained large language models can inject useful agronomic knowledge into Bayesian optimization for germplasm evaluation, particularly by improving early-stage genotype selection, and can also support optimization when genomic information is unavailable. As models better handle long genomic sequences together with passport information, large-language-model-guided Bayesian optimization may become a practical and explainable decision-support approach for agricultural optimization.

bioinformatics↗

BacteReason: A Reasoning Model for Antimicrobial Resistance Prediction

The rapid global spread of antimicrobial resistance (AMR) has placed unprecedented pressure on clinical decision-making. Machine learning predictors of antibiotic susceptibility exist, but their lack of mechanistic grounding limits credibility. We present BO_SCPLOWACTEC_SCPLOWRO_SCPLOWEASONC_SCPLOW, a reasoning large language model (LLM) that predicts bacterial susceptibility to a target antibiotic, together with a mechanistic rationale. BacteReason is obtained by fine-tuning an open-weight LLM on clinical susceptibility data augmented with rationales that explain the molecular mechanisms. These rationales are produced by a proprietary teacher LLM prompted to explain known susceptibility outcomes. The teacher is interfaced via TogoMCP with a collection of biomedical knowledge-graph databases, grounding each reasoning step in retrieved evidence. On an extrapolation benchmark, BO_SCPLOWACTEC_SCPLOWRO_SCPLOWEASONC_SCPLOW achieves a relative improvement of 43% over the untuned baseline and 38% over the same base LLM fine-tuned without rationales, demonstrating that reasoning supervision improves prediction accuracy.

bioinformatics↗

Biosynthesis of a major plant immunity hormone, salicylate, changed drastically during evolution of flowering plants

Salicylate (SA) is a major plant immunity hormone that activates immune responses against biotrophic pathogens. Between two known SA biosynthetic routes, the isochorismate synthase (ICS) and phenylalanine ammonia-lyase (PAL) pathways, which predominates in particular flowering plants has remained uncertain. We established a straightforward approach that directly quantifies the relative contributions of the ICS and PAL pathways and can also reveal an alternative, non-ICS/PAL route. In this approach, SA and shikimate (ShA), the precursor of SA in the ICS and PAL pathways, were metabolically labeled with [13C6]glucose in leaf tissue. We analyzed the LC-MS/MS data of the compounds using a metabolism-guided statistical model (the ICS-PAL model). This analysis allowed tracking of the origins of their ring and carboxyl carbons and, consequently, determination of the main SA biosynthetic routes. We surveyed SA biosynthetic routes in plants of the order Brassicales, other diverse eudicots, a monocot, magnoliids, and basal angiosperms. We found that the main SA biosynthetic routes changed at least twice during evolution of flowering plants: from a non-ICS/PAL pathway to the PAL pathway around the divergence time of monocots, and from the PAL pathway to the ICS pathway within Brassicales. Application of another metabolism-guided statistical model (the PKS-PAL model) to the SA data suggested that the non-ICS/PAL pathway involves a type III polyketide synthase (PKS). Typically, once a biosynthetic pathway is established for an important molecule, it is conserved in the subsequent lineage. SA biosynthesis in flowering plants took an unusual evolutionary path in which the pathways changed drastically multiple times. This unconventional evolutionary mechanism was employed for a major immunity hormone, likely due to rapid evolution of biotic environments, such as pathogens and insects that attack plants.

plant biology↗

Optimizing progeny allocation strategies in breeding schemes while updating genomic prediction models

Genomic selection has revolutionized breeding by enabling the early identification of superior individuals using genome-wide markers, enhancing breeding efficiency and accelerating variety development. Over the past decade, new selection and mating strategies -- leveraging optimization methods and other approaches -- have been introduced to improve various decision-making processes in breeding programs. However, optimizing breeding remains challenging when the positions and effects of quantitative trait loci are unknown. We developed a framework that optimizes breeding strategies while updating genomic prediction models during breeding schemes. By implementing intermediate model updates, we enabled re-optimization of allocation strategies based on updated predictions. Our simulations compared this approach with equal allocation and optimal cross selection methods across various selection intensities and genetic architectures. Results demonstrated our optimized allocation strategy significantly outperformed the other approaches under moderate to low selection intensities, particularly when combined with model updates. While genetic gains plateaued without updates, our approach enabled continuous improvement through the final generation. The framework showed exceptional robustness across different simulation conditions and better maintained genetic diversity while controlling changes in population structure. This confirms that optimized allocation strategies remain effective when using estimated marker effects rather than true effects, providing a practical framework for improving real-world breeding programs.

genomics↗

Ab-VS: Evaluating Large Language Models for Virtual Antibody Screening via Antibody-Antigen Interaction Prediction

We present Ab-VS-Bench, a new benchmark for evaluating large language models (LLMs) on antibody virtual screening (VS) tasks through natural language instructions. Unlike prior efforts that focus on structural annotation, binding prediction, or developability using frozen antibody models, Ab-VS-Bench targets the end-to-end VS workflow and leverages LLMs instruction-following capabilities. The benchmark comprises three core tasks inspired by small-molecule VS: (1) Scoring--predicting antibody-antigen binding affinity, (2) Ranking--ordering antibodies by affinity or thermostability, and (3) Screening--identifying high-affinity binders from large antibody libraries. We convert experimental datasets into instruction-tuning format and evaluate multiple model variants, including zero-shot LLMs, instruction-finetuned LLMs, and multimodal models enhanced with antibody-specific embeddings. Ab-VS-Bench provides a unified framework to benchmark LLMs for antibody discovery, aiming to catalyze progress in language-guided biotherapeutic design.

bioinformatics↗

Evolutionary Trade-off Between Stomatal Defense and Gas Exchange in Brassicaceae

Stomatal opening is crucial for gas exchange, but it unavoidably offers invasion by pathogens. In response, plants close stomata to prevent pathogen entry, while the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pto) produces coronatine (COR), a jasmonate (JA) mimic, to counteract this plant response. Here, we demonstrate that by COR, Pto exploits CYP707A1 activation in Arabidopsis thaliana, encoding an enzyme that degrades abscisic acid, essential for stomatal closure. Notably, COR-induction of CYP707A1 is absent in other Brassicaceae species, such as Capsella rubella and Eutrema salsugineum, rendering them resistant to Pto invasion. In contrast, in A. thaliana, CYP707A1 enables rapid stomatal opening at dawn in a JA-dependent manner, enhancing gas exchange and chlorophyll content, unlike C. rubella and E. salsugineum. Promoter-swap experiments confirm that the regulatory region of CYP707A1 underlies these evolutionary diversifications. Together, our study presents a mechanism underlying an evolutionary trade-off between stomatal defense and gas exchange.

plant biology↗

Emergence of isochorismate-based salicylic acid biosynthesis within Brassicales

Salicylic acid (SA) is a major defense phytohormone. In Arabidopsis thaliana, the isochorismate (IC) pathway is the primary route for pathogen-induced SA biosynthesis. First, the IC synthase (ICS) catalyzes the isomerization of chorismate to IC in chloroplasts. Second, the chloroplast-localized MATE transporter EDS5 appears to transport IC from chloroplasts to the cytosol. Cytosolic IC is then further converted to SA via the GH3 amino acid-conjugating enzyme PBS3. While this pathway is genetically well-characterized in A. thaliana, its evolutionary origin and conservation remain controversial. In this study, through comprehensive phylogenetic, structural, and functional analyses, we demonstrate that the IC pathway emerged within the Brassicales order in a time span between the divergence of Carica papaya and Capparis spinosa. The evolution of the IC pathway was driven by three key adaptations during the time span: (1) enhancement of ICS activity, (2) neofunctionalization of EDS5 after duplication of its ancestral gene, and (3) evolution of a PBS3, whose activity is specialized for glutamate-conjugation to IC. Structural modeling and functional assays reveal that an enhanced salt bridge network in ICS enhanced its activity. One of the duplicated genes, EDS5, acquired key amino acid substitutions in the C-lobe, which likely contributed to the EDS5 neofunctionalization. In addition, the functional PBS3 clade, including A. thaliana PBS3, is restricted to a Brassicales clade. Taken together, this study addresses the evolutionary trajectory of IC-based SA biosynthesis.

plant biology↗

Differentiable breeding: Automatic differentiation enables efficient gradient-based optimization of breeding strategies

MotivationDifferentiable programming frameworks like PyTorch and JAX revolutionized biological modeling. A foremost merit is that multiple components programmed separately can be put together so that the parameters are jointly optimized. Despite its proven value in agricultural applications, existing breeding simulators are non-differentiable, hindering integration into general deep learning systems. ResultsIn this paper, we present DiffBreed, a differentiable breeding simulator. Its performance was evaluated in gradient-based optimization of a progeny allocation strategy that maximizes the genetic gain. By utilizing gradient-based optimization, DiffBreed refined progeny allocation strategies, achieving superior genetic gains compared to a non-optimized equal allocation approach. These findings highlight DiffBreeds capacity to properly calculate gradient information through automatic differentiation. With its innovative design, DiffBreed is expected to transform future breeding optimization by integrating into modern deep learning workflows. AvailabilityThe proposed utomatic differentiation framework was implemented as the Python module "DiffBreed". This module and all the scripts used in this study, including the gradient-based optimization, are available from the "KosukeHamazaki/GORA-PT" repository on GitHub, https://github.com/KosukeHamazaki/GORA-PT. While the simulated datasets in the present study are available from the same repository, the optimized results by PyTorch were not shared in this repository due to the file sizes. Instead, all datasets, including the optimized ones, will be shared in the repository on Zenodo, https://doi.org/10.5281/zenodo.14046522.

bioinformatics↗

Leaf- and diverged shoot meristem programs shape the stem in rice

The stem is the shoot axis in seed plants and has been a primary target in breeding to regulate crop height. However, early processes of stem development remain elusive. Here we show that regulators for shoot meristems and leaves determine the node-internode pattern in rice. Mutants of KNOX1 genes OSH15 and OSH1, known to maintain shoot meristem indeterminacy1,2, showed dwarfism due to enlarged nodes and diminished internodes. These genes confine node differentiation by repressing leaf developmental regulator YABBY genes in internodal vasculatures. YABBY expression, which normally extends from leaves to nodes along vasculatures, promotes nodal vascular differentiation and limits stem elongation. It expands in knox1 mutants, and the loss of YABBY genes reverts their dwarfism. OSH15 also represses node-specific KNOX1 subclade genes OSH6 and OSH71 to allow internode elongation. Importantly, both YABBY and node-specific KNOX1 genes are required for pulvinus formation at the leaf base, further elaborating the nodal structure for gravitropism. Thus, intersections between leaf and sub-functionalized shoot meristem programs shape nodes and internodes along the stem. Phylogenetic analysis showed that KNOX1 sub-functionalization likely occurred in the progenitor of gymnosperms and angiosperms. Given that seed plants acquired their leaves independently from other vascular plant lineages3,4, the emergence of the node-internode pattern and KNOX1-YABBY regulatory module may be linked to seed plant leaf evolution.

plant biology↗

The kinetics and basal levels of the transcriptome response during Effector-Triggered Immunity in Arabidopsis are mainly controlled by four immune signaling sectors

To observe the transcriptome response during Effector-Triggered Immunity (ETI) without complications from any other pathogen factors or heterogeneously responding cell populations, we transgenically and conditionally expressed the Pseudomonas syringae effector AvrRpt2 in Arabidopsis leaves. We studied this ETI-specific, cell-autonomous transcriptome response in 16 exhaustively combinatorial genetic backgrounds for the jasmonate (JA), ethylene (ET), PAD4, and salicylate (SA) immune signaling sectors. Removal of some or all four sectors had relatively small impacts on the intensity of the overall ETI transcriptome response (1972 upregulated and 1290 downregulated genes). Yet, we found that the four signaling sectors strongly affect the kinetics of the ETI transcriptome response based on analysis of individual genes via time-course modeling and of the collective behaviors of the genes via a PCA-based method: the PAD4 sector alone and the JA;SA sector interaction (defined by the averaging model) accelerated the response, while the ET;SA sector interaction delayed it. The response acceleration by the PAD4 sector or the JA;SA sector interaction was consistent with their positive contributions to ETI measured by pathogen growth inhibition. The responsive genes overlapping between ETI and Pattern-Triggered Immunity (PTI) had distinct regulatory trends regarding the four sectors, indicating different regulatory circuits in upstream parts of ETI and PTI signaling. The basal mRNA levels of most ETI-upregulated genes, but not downregulated genes, were predominantly positively regulated by the PAD4;SA sector interaction. This detailed mechanistic decomposition of the roles of four signaling sectors allowed us to propose a potential regulatory network involved in ETI signaling.

systems biology↗

Commensal lifestyle regulated by a negative feedback loop between Arabidopsis ROS and the bacterial T2SS

Despite the plant health-promoting effects of plant microbiota, these assemblages also comprise potentially detrimental microbes. How plant immunity controls its microbiota to promote plant health under these conditions remains largely unknown. We found that commensal bacteria isolated from healthy Arabidopsis plants trigger diverse patterns of reactive oxygen species (ROS) production via the NADPH oxidase RBOHD that selectively inhibited specific commensals, notably Xanthomonas L148. Through random mutagenesis, we found that L148 gspE, encoding a type II secretion system (T2SS) component, is required for the damaging effects of Xanthomonas L148 on rbohD mutant plants. In planta bacterial transcriptomics revealed that RBOHD suppresses most T2SS gene expression including gspE. L148 colonization protected plants against a bacterial pathogen, when gspE was inhibited by ROS or mutation. Thus, a negative feedback loop between Arabidopsis ROS and the bacterial T2SS tames a potentially detrimental leaf commensal and turns it into a microbe beneficial to the host.

plant biology↗

Structural polymorphisms within a common powdery mildew effector scaffold as a driver of co-evolution with cereal immune receptors

In plants, host-pathogen coevolution often manifests in reciprocal, adaptive genetic changes through variations in host nucleotide-binding leucine-rich repeat immune receptors (NLR) and virulence-promoting pathogen effectors. In grass powdery mildew (PM) fungi, an extreme expansion of a RNase-like effector family, termed RALPH, dominates the effector repertoire, with some members recognized as avirulence (AVR) effectors by cereal NLR receptors. We report the structures of the sequence-unrelated barley PM effectors AVRA6, AVRA7 and allelic AVRA10/AVRA22 variants, which are detected by highly sequence-related barley NLRs MLA6, MLA7, MLA10, and MLA22, and of wheat PM AVRPM2 detected by the unrelated wheat NLR PM2. The AVR effectors adopt a common scaffold, which is shared with the ribonuclease (RNase) T1/F1-family. We found striking variations in the number, position, and length of individual structural elements between RALPH AVRs, which is associated with a differentiation of RALPH effector subfamilies. We show that all RALPH AVRs tested have lost nuclease and synthetase activities of the RNase T1/F1- family and lack significant binding to RNA, implying that their virulence activities are associated with neo-functionalization events. Structure-guided mutagenesis identified six AVRA6 residues that are sufficient to turn a sequence-diverged member of the same RALPH subfamily into an effector specifically detected by MLA6. Similar structure-guided information for AVRA10 and AVRA22 indicates that MLA receptors detect largely distinct effector surface patches. Thus, coupling of sequence and structural polymorphisms within the RALPH scaffold of PMs facilitated escape from NLR recognition and potential acquisition of diverse virulence functions.

plant biology↗

Heat-shock inducible clonal analysis reveals the stepwise establishment of cell fates in the rice stem.

The stem, consisting of nodes and internodes, is one of the major organs in seed plants. In contrast to other organs, however, processes of stem development remain elusive, especially when nodes and internodes are initiated. By introducing an intron into the Cre recombinase gene, we established a heat-shock inducible clonal analysis system in a single binary vector and applied it to the stem in the flag leaf phytomer of rice. With detailed characterizations of stem development, we show that cell fate acquisition for each domain of the stem occurs stepwise. Cell fates for a single phytomer and the foot (non-elongating domain at the stem base) were established in the shoot apical meristem by one plastochron before the leaf initiation. The fate acquisition for the node occurred just before the leaf initiation, separating cell lineages for leaves and stems. Subsequently, fates for the axillary bud were established in early leaf primordia. Finally, cells committed to the internode emerged from, at most, a few tiers of cells when the stem epidermis was at the 12[~]25 celled stage. Thus, the internode is the last part of the stem whose cell fate is established. This study provides a groundwork to unveil underlying molecular mechanisms in stem development and a useful tool for clonal analysis, which can be applied to various species.

plant biology↗

Dynamic decomposition of transcriptome responses during plant effector-triggered immunity revealed conserved responses in two distinct cell populations

O_LIRapid plant immune responses in the appropriate cells are needed for effective defense against pathogens. Although transcriptome analysis is often used to describe overall immune responses, collecting transcriptome data with sufficient resolution in both space and time is challenging. C_LIO_LIWe reanalyzed public Arabidopsis time-course transcriptome data obtained after a low-dose inoculation of a Pseudomonas syringae strain expressing the effector AvrRpt2, which induces Effector-Triggered Immunity (ETI) in Arabidopsis. Double-peak time-course patterns were prevalent among thousands of upregulated genes. We implemented a multi-compartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each gene. C_LIO_LIThe decomposed peaks revealed an "echoing" pattern: the peak times of the first and second peaks correlated well across most upregulated genes. We demonstrated that two peaks likely represent responses of two distinct cell populations, which respond either cell-autonomously or indirectly to AvrRpt2. Thus, the peak decomposition extracted spatial information from the time-course data. C_LIO_LIThe echoing pattern also indicated a conserved transcriptome response between two cell populations despite different elicitor types. WRKY transcription factors appeared to underlie the conserved transcriptome response. Activation of a WRKY network via different entry-point WRKYs could explain the conserved transcriptome response elicited by different elicitor types. C_LI

systems biology↗

Rice GLUCAN SYNTHASE-LIKE5 promotes Callose deposition in Anthers to maintain proper Male Meiosis Initiation and Progression

Callose is a plant cell-wall polysaccharide whose deposition is spatiotemporally regulated in various developmental processes and environmental stress responses. Appearance of callose in premeiotic anthers is a prominent histological hallmark for the onset of meiosis in flowering plants, whose biological role in meiosis is unknown till date. Here we show that rice GLUCAN SYNTHASE LIKE5 (OsGSL5), a callose synthase, localizes on the plasma membrane of pollen mother cells (PMCs), and is responsible for biogenesis of callose in anther locules through premeiotic and meiotic stages. In osgsl5 mutant anthers mostly lacking callose deposition, aberrant PMCs accompanied by aggregated, unpaired or multivalent chromosomes were frequently observed, and furthermore, a considerable number of mutant PMCs untimely progress into meiosis compared to wild type PMCs. Immunostaining of meiosis-specific protein PAIR2 in premeiotic PMCs revealed precocious meiosis entry in osgsl5 anthers. The findings of this study bestows new knowledge on function of callose in controlling timing of male meiosis initiation and progression, in addition to roles in microsporogenesis, in flowering plants.

developmental biology↗

Overexpression of NDR1 Leads to Pathogen Resistance at Elevated Temperatures

Abiotic and biotic environments influence a myriad of plant-related processes, including growth, development, and the establishment and maintenance of interaction(s) with microbes. As a driver of this signaling between plants and microbes, the role of plant hormones in both surveillance and signaling has emerged as a point of intersection between plant-abiotic and -biotic responses. In the current study, we elucidate a role for NON-RACE-SPECIFIC DISEASE RESISTANCE1 (NDR1) by exploiting effector-triggered immunity (ETI) to define the regulation of plant host immunity in response to both pathogen infection and elevated temperature. We generated time-series RNA sequencing data of WT Col-0, a NDR1 overexpression line, as well as ndr1 and ics1-2 mutant plants under elevated temperature. Not surprisingly, the NDR1-overexpression line showed genotype-specific gene expression changes related to defense response and immune system function. Interestingly, overexpression of NDR1 revealed a role for NDR1 in immune system function; specifically, we describe a mechanism that intersects with Pseudomonas syringae, type-III effector translocation, R-protein signaling complex stabilization, and sustained levels of SA at elevated temperature during ETI. The results described herein support a role for NDR1 in maintaining cell signaling during simultaneous exposure to elevated temperature and avirulent pathogen stressors. One-sentence summaryNDR1 is required for Pst-AvrRpt2 triggered ETI at elevated temperature.

plant biology↗