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Pharmacogenetics uses genetic testing to improve the safety and effectiveness of prescribed medicines, yet implementation at scale remains limited due to the absence of interoperable health IT solutions that integrate results into prescribing workflows. This study aimed to develop and validate open data standards for pharmacogenetic results to enable interoperability across healthcare systems. A baseline data model was constructed using the open standard openEHR by synthesising literature, genomic sequencing outputs, and international data specifications, and refined through iterative workshops with the Global Alliance for Genomics and Health. The model underwent two rounds of structured peer review involving 24 experts from 10 countries. Mapping to HL7 FHIR was evaluated using both manual and automated approaches, including the FHIR-Connect tool. The resulting standardised pharmacogenetic data model separates test results from therapeutic implications and incorporates recognised terminologies such as SNOMED CT and HGNC. It achieved international consensus and is published on the openEHR Clinical Knowledge Manager platform. Mapping to HL7 FHIR demonstrated bidirectional information flow within healthcare systems, with automated mapping enabling scalable and reusable transformations. This work provides a framework for storing and exchanging pharmacogenetic test results, supporting semantic harmonisation, interoperability, and integration with clinical decision support systems. Open data standards for pharmacogenetic test results therefore offer a foundation for scalable implementation of pharmacogenetics in routine clinical practice.

Genome-wide association studies in complex polyploids are hindered by genotyping ambiguity and allele dosage complexity. Here we present KMERIA, a k-mer-based framework specifically designed to address these challenges, enabling efficient genotyping and robust association mapping in complex polyploid genomes. Rigorous benchmarking with simulated and empirical datasets demonstrates that KMERIA surpasses existing methods in accuracy and statistical power. By applying KMERIA to 290 wild sugarcane (Saccharum spontaneum) accessions and integrating a 15-accession graph pangenome to capture structural variations, we identified new genes regulating sucrose biosynthesis (SsMGT) and tillering (for example, SsERF14, SsNGA5, SsNAC, SsARF8, SsLOG and SsSCR). These findings elucidate the genetic architecture of yield-related traits and provide actionable targets for sugarcane breeding. Collectively, KMERIA bridges a critical methodological gap in polyploid genomics, while our graph-pangenome integration provides a powerful framework for deciphering genotype-phenotype relationships in crops with complex architectures.

Genomics, including all molecular omics, is driven by molecular data, while phenomics and enviromics rely on phenotypic and environmental data. Yet phenotyping is often conducted under poorly characterized environments, limiting the interpretation of phenotypic variation and constraining genetic gain. Integrating high-throughput phenotyping with envirotyping is hence vital to resolve genomic effects. This perspective introduces phenomics-enviromics (PE) crosstalk as a framework for coordinated data collection and integration to advance omics and precision plant breeding. Satellites, unmanned aerial and ground vehicles, and controlled indoor facilities, combined with AI-assisted typing technologies and modeling, are establishing the basis for synchronous, high-throughput PE crosstalk to enhance interpretability, prediction, and crop resilience.

Genomic signatures-taxon-specific patterns in nucleotide composition-are widely used for taxonomic assignment and comparative genomics, yet their genome-wide pervasiveness across Telomere-to-Telomere assemblies, particularly within functionally diverse and highly repetitive regions, remains undercharacterized. We address this gap with an alignment-free, [Formula: see text]-mer-based analysis using Frequency Chaos Game Representations (FCGRs) across the human genome and three additional eukaryotes from distinct kingdoms. First, by combining qualitative inspection of FCGR landscapes with quantitative distance benchmarking, we show that each species exhibits a stable genomic signature across most chromosomes, with localized departures concentrated in regions enriched for short and long tandem repeats. Then, we introduce two computational pipelines that automatically select a short, contiguous representative genomic segment (500 Kbp) per genome and use it as a proxy to quantify intragenomic variation. Using DSSIM on a [0,1] scale, 80% of 500 Kbp segments in the human genome lie within 0.24 of the representative; segments exceeding this threshold align with tandem-repeat-dense loci. Leveraging these representatives in downstream tasks yields practical gains-for example, one-nearest-neighbor taxonomic classification improves by 7% relative to choosing a random segment. Finally, we provide kCGR-Diff, a graphical tool that enables side-by-side visualization and quantitative comparison of FCGR-based genomic signatures for sample or user-provided sequences, facilitating exploratory analyses of intragenomic variation within and across species. Collectively, our results provide extensive qualitative and quantitative evidence that [Formula: see text]-mer-based genomic signatures are pervasive at genome scale while varying predictably in repeat-dense regions, and they introduce practical methods and software for proxy selection and comparative analysis.

Species identification from highly degraded DNA remains a major challenge across ecology, conservation genetics, wildlife forensics, and museum science, where samples are often scarce, contaminated, and embedded in complex matrices. Under these conditions, standard reference-based and metagenomic classifiers are prone to false-positive assignments, particularly when ultra-fragmented DNA and conserved genomic regions are not explicitly accounted for. Here, we present a damage-aware next-generation sequencing (NGS) workflow for conservative species identification from minute quantities of highly degraded DNA, designed to minimize misclassification in low-input and damage-rich datasets. The workflow integrates micro-sampling, half-uracil-DNA-glycosylase (half-UDG) library preparation, PCR duplicate removal, multi-genome mapping against a curated reference panel, and a post-mapping read-ubiquity classifier that distinguishes species-specific reads from those shared across conserved loci. Using collagen-rich substrates as a proof-of-concept, we demonstrated accurate species attribution from samples as small as 1 mm2, including mixtures and mineral-containing matrices. The workflow reliably identifies dominant biological sources, reduces false-positive assignments driven by conserved genomic regions, and remains robust to common physical and chemical treatments such as swelling, heating, and plaster addition. Overall, this study provides a proof-of-concept framework for conservative species identification in challenging degraded DNA contexts. The workflow may be adaptable to a broader range of degraded DNA contexts-including wildlife monitoring, regulatory enforcement, forensic investigations, and the analysis of processed biological materials-although further validation across diverse matrices will be required.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune-mediated destruction of intrahepatic bile ducts, leading to fibrosis, cirrhosis, and liver failure. Ursodeoxycholic acid remains the first-line treatment, but up to 40% of patients respond inadequately and continue to experience fatigue and pruritus. This therapeutic gap has recently been addressed by the approval of two new drugs, elafibranor and seladelpar, which activate peroxisome proliferator-activated receptors (PPARs). This review explores recently unveiled molecular mechanisms underlying the effectiveness of PPAR-targeting drugs in PBC, focusing on their effects on cellular immune regulation, bile acid production and toxicity, and hepatic fibrosis. Additionally, we examine current knowledge and ongoing challenges that will influence the roles of PPAR agonists in improving PBC treatment.

To standardise the diagnostic criteria for cerebral palsy (CP) in China by resolving key ambiguities surrounding the timing of brain injury, the definition of non-progressiveness and the role of genetic aetiologies. A modified Delphi process was conducted in 2025 by the Rehabilitation Subspecialty Group of the Chinese Pediatric Society. Thirty-three national experts in paediatric neurology, rehabilitation, genetics and epidemiology participated. The process included literature review, iterative statement drafting and two rounds of anonymous voting. Consensus was defined as ≥80% agreement. Three diagnostic pillars were established: (1) a non-progressive injury to the developing brain occurring from the embryonic period through age 3; (2) non-progressive nature is defined by the absence of regression of previously acquired motor milestones through age 5 and (3) genetic factors are integral to CP pathogenesis and may justify classification as 'CP due to genetic variation' when specific criteria are met. Cerebral MRI, General Movements Assessment and Hammersmith Infant Neurological Examination were highlighted as key tools for early diagnosis. This updated expert consensus aligns national CP diagnostic criteria with current advances in neurodevelopmental and genomic science. It supports early, accurate diagnosis, guides genetic evaluation and promotes harmonised clinical practice across Chinese healthcare systems.

Variants in TPMT and NUDT15 genes that affect thiopurine metabolism can guide personalized dosing to minimize toxicity. Decreased or no appreciable NUDT15 activity demonstrates impaired breakdown of active thiopurine metabolites which can lead to severe adverse events including potentially life-threatening myelosuppression. Recently, the NUDT15*6 allele was re-classified from having uncertain function to no function by the Clinical Pharmacogenetics Implementation Consortium. Here, we present a pediatric patient with a NUDT15*1/*6 genotype who experienced significant thiopurine-induced myelosuppression. The patient is a 4-year-old female with standard risk-average precursor B-cell acute lymphoblastic leukemia treated per AALL1731. Exome sequencing determined TPMT*1/*1 (normal metabolizer) and NUDT15*1/*6 (indeterminate metabolizer). After 75 mg/m2/day mercaptopurine, myelosuppression necessitated a three-week delay prior to the next phase of therapy. With 60 mg/m2/day thioguanine in a subsequent phase of therapy, she was admitted twice for fever and neutropenia. In the final phase of therapy, mercaptopurine at standard dosing of 75 mg/m2/day caused severe neutropenia and thrombocytopenia with elevated metabolite levels that required stopping mercaptopurine. After neutrophil recovery, a trial of 50% standard dosing was not tolerated and her dose was reduced to 27%, which was tolerated. Among 339 patients with cancer, sequencing revealed an allele frequency of 0.88% for NUDT15*6. In a larger cohort sequenced for suspicion of rare genetic disease, the frequency of NUDT15*6 was 0.15% among 1011 unrelated individuals. This brief report supports the recent update that patients with the NUDT15*1/*6 genotype should be classified as intermediate metabolizers.

Probiotic supplements are marketed for diverse health benefits, yet species inclusion often lacks functional rationale. Our survey of 352 over-the-counter probiotic products available in the USA revealed 36 unique microbial species. However, there is no clear link between species inclusion and the intended health benefit. Here, to address this gap, we developed HaPaPro, a collection of 1,012 genome-scale metabolic models spanning pathogenic, probiotic and host-associated bacteria, constructed from publicly available genome sequences. Flux balance analysis revealed that probiotic species fail to capture the metabolic diversity of host-associated microbes. Focusing on vaginal health, we computationally identified vaginal microbes with metabolic profiles overlapping Gardnerella vaginalis. In vitro spent media assays using 11 vaginal isolates showed variable inhibition of G. vaginalis, primarily driven by D-lactic acid production, which was also produced by non-Lactobacillus species. These findings highlight the need for function-based probiotic design and demonstrate a scalable framework integrating metabolic modelling with experimental validation.

Plasmodium falciparum remains a major cause of mortality in malaria-endemic regions, and strain-specific immunity limits vaccine efficacy. The 6-cysteine proteins Pf12 and Pf41 are proposed blood-stage vaccine candidates, yet their diversity and antigenicity in asymptomatic carriers are poorly defined. Genetic variation and natural selection pressure were analyzed in 172 P. falciparum isolates from asymptomatic individuals in Tanzania. Genomic DNA extracted from dried blood spots was amplified by PCR and subsequently sequenced to evaluate genetic diversity. IgG responses to recombinant Pf12 and Pf41 were quantified using a protein microarray. Statistical analyses included Spearman's correlation to assess antibody associations and unpaired t-tests to compare IgG levels between parasite-positive and parasite-negative individuals. Both genes exhibited low nucleotide diversity (pf12 &#x3c0;&#x2009;=&#x2009;0.00042&#x2009;&#xb1;&#x2009;0.00007; pf41 &#x3c0;&#x2009;=&#x2009;0.00061&#x2009;&#xb1;&#x2009;0.00004) and negative Tajima's D values suggest that both genes are under selective constraints, consistent with purifying or directional selection. Neutrality test indicated an excess of rare variants consistent with recent population expansion. Haplotype network showed limited regional differentiation, supporting strong conservation. Pf12 and Pf41 elicited high IgG seropositivity (97.7% and 98.3%), with strongly correlated antibody levels (&#x3c1;&#x2009;=&#x2009;0.721, p&#x2009;<&#x2009;0.001). A predominant Pf41 substitution, S232R (47.8%), and rare Asn/His variants (0.6%) were detected. Overall, both proteins display limited polymorphism and robust IgG recognition, features consistent with exposure-driven immunity. These findings highlight conserved merozoite antigens that warrant further investigations for their biological relevance and vaccine potential, particularly to determine their functional role in protective immunity.

The overall goal of this study was to reveal the genetic basis of semen production and quality traits in Italian Brown Swiss dairy cattle. Data consisted of 15,037 ejaculates from a total of 1,591 bulls. Semen traits evaluated were volume, concentration, number of spermatozoa, total motility, and progressive motility. A subset of 1,102 bulls also had records for sire conception rate, as a measure of reproductive success. We estimated the heritability and repeatability of semen traits and their genetic correlations with sire conception rate using univariate and bivariate animal models. We also identified candidate genes for semen traits using single-step genomic scans with 438k SNP markers and revealed gene networks and biological pathways through functional gene-set analyses. Heritabilities ranged from 0.04 for progressive motility to 0.23 for volume, indicating the possibility of improving these traits through selective breeding. Repeatabilities were considerably higher than the heritabilities, especially for sperm motility, indicating that both non-additive effects and the permanent environment significantly affect bull fertility. We found low to moderate genetic correlations among sperm traits, and of particular interest, high genetic correlations between sperm motility and sire conception rate, indicating the predictive values of these traits for sire reproductive success. Genomic scans revealed regions on BTA4 and BTA11 highly associated with total and progressive motility. These regions harbor genes, such as RPS27A, CCDC88A, CFAP36, SPMIP4, and DNAAF1, that are all directly implicated in sperm motility. The gene-set analyses revealed functional terms related to sperm biology, male fertility, fertilization, and the immune system, among others. Overall, our study contributes to a better understanding of the genetic basis of dairy bull fertility. In addition, our findings may guide the development and deployment of novel strategies for improving service sire fertility in Brown Swiss cattle.

Perihilar cholangiocarcinoma (pCCA) frequently presents as an indeterminate perihilar biliary stricture. The diagnosis is often delayed or uncertain because of the limited sensitivity of conventional endobiliary sampling and blood-based markers, especially in patients with additional confounding conditions such as primary sclerosing cholangitis (PSC). This diagnostic ambiguity can significantly impact clinical outcomes as timely detection and accurate classification are critical for referral and curative-intent treatment. As such, research focused on advancing diagnostic methodologies is a priority. pCCA has a distinct proteomic signature, pattern of activated signaling cascades, epigenetic modifications, and metabolic interactions within its anatomic niche. Recent advances in omics-based diagnostics have leveraged these biological features to identify biomarkers for accurate pCCA diagnosis. In this review, we summarize emerging evidence for omics-based diagnostics in pCCA using clinically accessible samples, including biliary brushings, bile and serum/plasma samples. We discuss the key aspects of pCCA biology that form the foundation for development of novel techniques including glyco-/phospho-/proteomic, genomic, methylomic, metabolomic, and lipidomic analyses as well as multiomic approaches. We conclude by outlining how artificial intelligence may help integrate the data into diagnostic algorithms and identifying areas requiring further investigation to advance these diagnostics into routine clinical practice.

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith-Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9&#x2009;weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: -4.04, 95% confidence interval: -6.89 to -1.18, P&#x2009;=&#x2009;0.006, Hedges' g&#x2009;=&#x2009;0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 .

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Objectives were to evaluate the effects of replacing sulfate (STM) with hydroxychloride (HTM) sources of Cu, Mn, and Zn on health, reproduction, and survival in dairy cows. One-hundred and 41 Holstein cows were stratified by parity group prepartum as nulliparous or parous cows and, within parity, nulliparous cows were blocked by genomic breeding value for ECM yield and parous cows by recently completed lactation 305-d ECM. Within block, cows were assigned to STM or HTM, and prepartum diets contained (mean &#xb1; SD) 15 &#xb1; 1, 58 &#xb1; 2, and 66 &#xb1; 3 mg/kg of diet DM as Cu, Mn, and Zn, respectively, whereas postpartum diets contained 19 &#xb1; 3, 65 &#xb1; 15, and 77 &#xb1; 11 mg/kg diet DM as Cu, Mn, and Zn, respectively. Treatments were fed from 246 d of gestation to 105 DIM. Concentrations of nonesterified fatty acids (NEFA), BHB, haptoglobin, and ceruloplasmin were measured in plasma and those of total Ca (tCa) were measured in serum. Diseases were diagnosed in the first 105 d postpartum and survival was evaluated until 305 DIM. The estrous cycle of cows was synchronized and artificial insemination (AI) was performed on d 87 postpartum. On d 19 after AI, serum was analyzed for progesterone and blood mononuclear cells and cervical cells were analyzed for mRNA for interferon-stimulated genes (ISG). Treatment did not affect the concentrations of NEFA, BHB, tCa, and progesterone in blood. Feeding HTM reduced the concentrations of haptoglobin in the first 19 d postpartum (40.0 &#xb1; 9.1 vs. 25.7 &#xb1; 5.0 &#xb5;g/mL) and that of ceruloplasmin only on d 6 postpartum (0.64 &#xb1; 0.03 vs. 0.58 &#xb1; 0.03 mg/mL). Feeding HTM reduced the risk of retained placenta (11.5 &#xb1; 6.3 vs. 3.8 &#xb1; 2.3%) and tended to reduce the risks of clinical (16.4 &#xb1; 9.7 vs. 4.0 &#xb1; 2.9%) and subclinical endometritis (29.8 &#xb1; 9.2 vs. 16.4 &#xb1; 5.7%). Cows fed HTM tended to have reduced rate (adjusted hazard ratio = 0.58; 95% CI = 0.33-1.04) and reduced risk of morbidity (51.7 &#xb1; 9.1 vs. 32.7 &#xb1; 7.1%) during first 105 d postpartum compared with feeding STM. Feeding HTM increased the relative expression of ISG by 1.7 to 2.0-fold in blood mononuclear cells on d 19 after AI in pregnant cows compared with STM; however, treatment did not affect the expression of ISG on cervical cells. Rate of pregnancy did not differ between treatments, but HTM tended to increase the proportion of pregnant cows by 305-d postpartum (68.8 &#xb1; 5.7 vs. 82.8 &#xb1; 4.7%) partially attributed to the reduced proportion of cows designated as do not inseminate (25.6 &#xb1; 5.3 vs. 9.8 &#xb1; 3.6%). Also, HTM reduced the rate (adjusted hazard ratio = 0.44; 95% CI = 0.20-0.96) and risk of leaving the herd by 305-d postpartum from 26.5 &#xb1; 9.6 in STM to 11.9 &#xb1; 5.0%. Replacing sulfate sources of Cu, Mn, and Zn with hydroxychloride sources of same trace minerals benefited early lactation health of cows in early postpartum which carried out to benefit reproduction and survival.

Despite notable differences in cancer incidence and outcomes, fewer American Indians have participated in cancer research and genomic testing relative to their population size. Contributing factors include historical scientific mistrust, lack of culturally appropriate research methodologies, and limited access. With the launch of a cancer genomic sequencing trial in American Indians from the Southwestern United States (US), clinicians and staff encountered challenges engaging patients, recognizing the complexity of research in this population. We describe a novel approach to educate study team members regarding genomic cancer testing and research in American Indian populations. Clinical faculty and staff investigators participated in (1) hands-on experiential workshops related to core beliefs and healthcare in American Indians and (2) the development of provider-facing educational materials. After participation in the workshops, investigators, including American Indian researchers, created two sets of provider-facing materials and implemented them in clinic. The first provided a summary detailing trial eligibility, procedures, and privacy safeguards. The second outlined topics fostering respectful engagement of American Indians in research, outlining core beliefs including the importance of family and community in decisions, a framework of inherent cycles in human life and nature, the importance of visual aids, and the complementary nature of traditional healing. An approach incorporating cultural training for clinicians and staff is feasible when engaging American Indians of the Southwestern US in genomic research. This methodology may serve as a model for future initiatives to engage with American Indians in cancer research and in both clinical and research related genomic testing.

Spain has recently included rotavirus vaccines (RV1 [Rotarix] and RV5 [RotaTeq]) into the National Immunization Programme, following a period of exclusive private availability. This study aimed to analyze rotavirus molecular epidemiology and clinical outcomes during the period preceding routine nationwide vaccination, when vaccinated and unvaccinated children coexisted. This prospective study analyzed 647 rotavirus-positive stool samples with associated clinical-epidemiological data from patients with rotavirus gastroenteritis (RVGE) collected between December 2021 and June 2023. Among children aged 0-4&#xa0;years with RVGE, incomplete or absent vaccination (adjusted-OR:3.92) and having pre-existing medical conditions (adjusted-OR: 17.67) were significant risk factors for RVGE-related hospitalisation (p&#x2009;<&#x2009;0.001). Equine-like-G3P[8] (EQL-G3) was the predominant genotype (62.4%). Despite its predominance, EQL-G3 was not associated with vaccination status or an increased risk of hospitalisation among RV-positive cases. Among vaccinated children, EQL-G3 strains were more frequent in RV1 recipients (p&#x2009;=&#x2009;0.012), while typical G3P[8] strains predominated in RV5 recipients (p&#x2009;<&#x2009;0.001). Whole-genome analyses identified NSP2 mono-reassortants, bovine-like NSP4 genes and potentially immunologically relevant mutations at antigenic epitopes, highlighting substantial genomic diversity. Overall, genotype distribution was largely similar between vaccinated and unvaccinated children, providing no evidence that viral genotype drives disease severity among RV-positive cases. Our findings reinforce the protective effect of full rotavirus vaccination in reducing hospitalizations, regardless of circulating genotypes. Nonetheless, given the observed genetic diversity and signals of reduced cross-protection of RV1 against EQL-G3 strains, continued and expanded molecular surveillance is essential to improve understanding of rotavirus diversity and to contextualize circulating genotypes within their clinical relevance over time.

Microbial methanogenesis is a major contributor to global warming, and methane fluxes represent a loss of energy and electrons from industrial ecosystems. The chemical space of methane control strategies is still underexplored. Most known methanogenesis inhibitors target methanogenic archaeal enzymes. However, interference with the exchange of syntrophic electron carriers (H2 or formate) in methanogenic systems presents an additional target for methane control. Here, we show that hypophosphite (H2PO2-), an inorganic formate analogue, is a potent and selective inhibitor of syntrophic methanogenesis versus primary fermentation in rice field sediments and cattle rumens. Hypophosphite is also generally recognized as safe and relatively nontoxic to plants and animals. Genetic screens and physiological assays in the model methanogen Methanococcus maripaludis S2 implicate formate metabolism as the target of hypophosphite inhibition. Currently, there is no known biological pathway for anaerobic hypophosphite oxidation, and hypophosphite is stable in anoxic sediments for weeks to months. Given its widespread natural occurrence, we propose that hypophosphite may modulate the carbon cycle in natural environments. Taken together, our results suggest that hypophosphite could be used as a safe, inexpensive strategy for methane control in syntrophic methanogenic ecosystems.

Thymic carcinoma, thymoma, and thymic neuroendocrine tumors are rare malignancies with limited treatment options in advanced stages. Immune checkpoint inhibitors (ICIs) have shown preliminary activity in thymic tumors, although their clinical benefit and toxicity profile remain incompletely defined. We retrospectively analyzed patients with thymic tumors treated with ICIs at MD Anderson Cancer Center from 2010 to 2024. Clinical characteristics, molecular profiles, treatment details, immune-related adverse events (irAEs), and survival outcomes were collected. The primary objective was ICI safety. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Cox regression identified predictors of survival. Forty-two patients were analyzed (median age, 59 years; 55% male), comprising 29 thymic carcinomas, 8 thymomas, and 5 neuroendocrine tumors. ICIs were administered as monotherapy (55%) or combinations (45%), most commonly anti-PD-1 agents (86%). IrAEs occurred in 60% overall and in all patients with thymoma. Grade &#x2265;3 irAEs developed in 19%, including one treatment-related death from pneumonitis. Common irAEs included fatigue, rash, and musculoskeletal symptoms. Notable neuromuscular syndromes included concurrent myasthenia gravis and myocarditis in thymoma. Among 37 RECIST-evaluable patients, ORR was 21%, and DCR was 78%. Median PFS was 6.5 months, and median OS was 9.1 months. Any-grade irAEs were associated with reduced mortality risk (HR, 0.30). TP53 mutations and lung metastases predicted worse OS, whereas CDKN2A alterations correlated with improved OS. ICIs demonstrated preliminary activity in thymic tumors but were associated with substantial toxicity, especially in thymoma. Biomarker-driven patient selection and vigilant irAE monitoring are needed.