Genomic Knowledge Research Articles

Adaptations of Rice Seed Germination to Drought and Hypoxic Conditions: Molecular and Physiological Insights

Seed germination is crucial for plant survival, crop stand establishment, and achieving optimal grain yield. The main objective of this review is to explore the physiological and molecular mechanisms governing rice seed germination under aerobic (water stress) and anaerobic (hypoxic) conditions in direct-seeded rice (DSR) systems. Moreover, it discusses the recent genomic advancements and innovations to improve rice seed germination. Here, we discuss how coleoptile and mesocotyl elongation plays a vital role in anaerobic germination (AG) and the function of raised antioxidants, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in maintaining Reactive Oxygen Species (ROS), and malondialdehyde (MDA) homeostasis for stabilizing seed germination in water-scarce conditions. This study comprehensively highlights the functions and dynamics of phytohormones—GA (gibberellic acid) and ABA (abscisic acid)—key regulatory genes, transcription factors (TFs), key proteins, and regulatory metabolic pathways, including glycolysis, the pentose phosphate pathway (PPP), and the tricarboxylic acid cycle (TCA), in regulating seed germination under both conditions. Conventional agronomic and cultural practices, such as seed selection, seed priming, seed coating, and hardening, have proven to improve seed germination. Moreover, the utilization of molecular and novel approaches—such as clustered regularly interspaced short palindromic repeat (CRISPR-Cas9) mediated genome editing, marker-assisted selection (MAS), genome-wide associations studies (GWAS), single nucleotide polymorphisms (SNPs), multi-omics, RNA sequencing—combined with beneficial quantitative trait loci (QTLs) has expanded knowledge of crop genomics and inheritance. These advancements aid the development of specific traits for enhancing seed germination in DSR.

Anxiety, depression and fear of cancer recurrence in uveal melanoma survivors and ophthalmologist/oncologist communication during survivorship in France – protocol of a prospective observational mixed-method study

BackgroundQuality of life (QoL) in patients undergoing surveillance for uveal melanoma (UM) can be affected by psychological sequelae. Fear of cancer recurrence (FCR) may be acute especially when prognostication indicates an increased risk of metastatic recurrence. Communication with an ophthalmologist or oncologist can then play a key role in impacting QoL.MethodsIn this prospective study co-designed with patient’s partners and using a mixed-method approach, 250 patients at high versus low risk of metastatic recurrence are recruited in a national UM reference centre in France. At T1, after the 6-months post-treatment surveillance visit, dyads of clinicians and eligible patients complete a questionnaire to assess their respective experience of the communication during that consultation. Patients also complete questionnaires assessing their health literacy, information preference, and satisfaction with the information received (EORTC QLQ-INFO25), genomic testing knowledge, genomic test result receipt, satisfaction with medical care (EORTC PATSAT-C33), perceived recurrence risk, anxiety and depression (HADS), fear of cancer recurrence (FCRI) and quality of life (EORTC QLQ-C30 and QLQ-OPT30). At 12-months post-treatment (T2), patients complete again the HADS, FCRI, EORTC QLQ-C30 and QLQ-OPT30. Multilevel analyses will assess the effect of satisfaction with the information received on FCR and QoL accounting for the clinicians’ and patients’ characteristics. In-depth interviews planned sequentially with ≈25 patients will deepen understanding of patients’ care experience.DiscussionAs information on prognosis based on medical parameters becomes widely integrated into oncology practice, this study will highlight UM survivors’ information expectations and satisfaction with communication, and its effect on FCR and QoL. Culturally adapted recommendations for doctor-patient communication will be provided for contexts of oncology surveillance involving poor prognosis in cases of recurrence.Trial registrationNCT06073548 (October 4, 2023).

Survey to identify barriers and enablers to implementation of genomics in pharmacy practice across healthcare sectors in a rural community

Abstract Introduction The potential for genomics to improve patient outcomes is being harnessed via national strategy to embed genomic testing into NHS practice, and drive use of precision medicines and pharmacogenomics1. The national pharmacy genomics education and training strategic framework aims to empower the pharmacy workforce, across all sectors, to use genomics to support medicines optimisation2. Cornwall, a rural and coastal county, has areas of marked deprivation with poorer health outcomes3 and challenges in recruiting and retaining healthcare professionals. It is key that rural/coastal communities have equitable access to genomic services and expertise to avoid exacerbating pre-existing health inequalities. Aim To identify barriers and enablers to the implementation of genomics into pharmacy practice in a rural community. Methods Pharmacists and pharmacy technicians working in Cornwall were eligible to participate. An anonymised survey was compiled via Microsoft Forms of closed, multiple choice and optional open questions. Following piloting, the survey link was disseminated via email by pharmacy leaders in community pharmacy, primary and secondary care in May 2024. Responses were stored securely via NHS password protected IT systems and analysed via quantitative and thematic analysis. As this project is defined as a service evaluation, according to the UK NHS Health Research Authority, ethical approval was not required. Results Fourteen pharmacists and 7 pharmacy technicians participated, from primary and secondary care and community hospitals, with no participants from community pharmacy. Seven had received prior training in genomics (teaching sessions (n=5), webinars (n=1), podcasts (n=1), articles in journals (n=2)). One participant had received formal undergraduate training. Key barriers to the implementation of genomics included a lack of education and training (n=5), perceived cost of genomic testing (n=2), difficulty in accessing genomic services (n=1) and lack of expert panels (n=1). It was also felt that genomics services were limited to secondary/tertiary care (n=2). Respondents stated that the rural location impacted the availability of face-to-face training and resources to support training (n=17). Key enablers were the opportunity for precision prescribing (n=8), and improved patient outcomes (n=7). Genomics education and training (n=5) and resources to support training (n=11) were viewed as being pivotal to supporting the mainstreaming of genomics. Discussion and conclusion Participants were keen to further their genomics knowledge, with a preference for face-to-face training. Respondents also highlighted the need for allocated resources to support training. As emphasised in the strategic framework2, workforce upskilling is vital to the successful mainstreaming of genomics, particularly when the majority of pharmacy staff had not received any formal training. There were no participants from community pharmacy, indicating a requirement to further explore barriers and enablers in this cohort. Community pharmacy staff may be reluctant to participate if they perceive genomics to relate solely to secondary/tertiary care. Survey methodology also limited the detail that could be obtained from respondents. This provides helpful preliminary insights on barriers and enablers to genomics implementation into pharmacy practice in rural/coastal areas. Themes could be further explored via semi-structured interviews, with the aim of shaping interventions necessary to ensure equitable provision of genomics services and expertise to these communities.

Disparities in Genetic Management of Breast and Ovarian Cancer Patients.

Hereditary breast and ovarian cancer syndrome (HBOC) is most often caused by pathogenic variants in the BRCA1 or BRCA2 genes. Guidelines exist for genetic testing in patients at high risk, yet significant disparities in genetic testing and management remain. These disparities result in missed opportunities for cancer prevention and treatment. This review details the multiple layers of disparities in genomic knowledge, testing referral, completion, and posttesting risk reduction for at-risk populations. A comprehensive search of the PubMed database was conducted in September 2023 for studies addressing disparities at all points of HBOC risk assessment and risk reduction. Disparities in genomic knowledge, referral and testing, and in cancer risk reduction exist by race, ethnicity, insurance status, socioeconomic status, age, and care setting in the United States. Many mitigation strategies have been explored with some success. Each component contributes to a "leaky pipe" in BRCA testing and management whereby patients eligible for intervention trickle out of the pipe due to inequities at each step. Implementation of proven strategies aimed at disparity reduction in this setting is essential, as well as additional strategy development. This review provides clinicians with a comprehensive understanding of disparities in the identification and management of individuals at risk for or diagnosed with HBOC and strategies to reduce disparities in their own practice.

Learning Heterogeneous Relation Graph and Value Regularization Policy for Visual Navigation.

The goal of visual navigation is steering an agent to find a given target object with current observation. It is crucial to learn an informative visual representation and robust navigation policy in this task. Aiming to promote these two parts, we propose three complementary techniques, heterogeneous relation graph (HRG), a value regularized navigation policy (VRP), and gradient-based meta learning (ML). HRG integrates object relationships, including object semantic closeness and spatial directions, e.g., a knife is usually co-occurrence with bowl semantically or located at the left of the fork spatially. It improves visual representation learning. Both VRP and gradient-based ML improve robust navigation policy, regulating this process of the agent to escape from the deadlock states such as being stuck or looping. Specifically, gradient-based ML is a type of supervision method used in policy network training, which eliminates the gap between the seen and unseen environment distributions. In this process, VRP maximizes the transformation of the mutual information between visual observation and navigation policy, thus improving more informed navigation decisions. Our framework shows superior performance over the current state-of-the-art (SOTA) in terms of success rate and success weighted by length (SPL). Our HRG outperforms the Visual Genome knowledge graph on cross-scene generalization with ≈ 56% and ≈ 39% improvement on Hits@ 5* (proportion of correct entities ranked in top 5) and MRR * (mean reciprocal rank), respectively. Our code and HRG datasets will be made publicly available in the scientific community.

Chromosome-level genome assembly of Megachile lagopoda (Linnaeus, 1761) (Hymenoptera: Megachilidae)

Megachile is one of the largest bee genera, including nearly 1,500 species, but very few chromosome-level assemblies exist for this group or the family Megachilidae. Here, we report the chromosome-level genome assembly of Megachile lagopoda collected from Xizang, China. Using PacBio CLR long reads and Hi-C data, we assembled a genome of 256.83 Mb with 96.08% of the assembly located on 16 chromosomes. Our assembly contains 266 scaffolds, with a scaffold N50 length of 15.6 Mb, and BUSCO completeness of 99.20%. We masked 27.10% (69.61 Mb) of the assembly as repetitive elements, identified 459 non-coding RNAs, and predicted 11,157 protein-coding genes. This high-quality genome of M. lagopoda represents an important step forward for our knowledge of megachilid genomics and bee evolution overall.

Interpretable deep cross networks unveiled common signatures of dysregulated epitranscriptomes across 12 cancer types

Cancer is a complex and multifaceted group of diseases characterized by uncontrolled cell growth that leads to the formation of malignant tumors. Recent studies suggest that N6-methyladenosine (m6A) RNA methylation plays pivotal roles in cancer pathology by influencing various cellular processes. However, the degree to which these mechanisms are shared across different cancer types remains unclear. In this study, we analyzed an expansive array of 167 m6A epitranscriptome profiles covering 12 distinct cancer types and their originating normal tissues. We trained 12 distinct, cancer type-specific interpretable deep cross network models, which successfully distinguish between specific pairs of normal and cancer m6A contexts using integrated information from both the sequences and curated genomic knowledge. Interestingly, cross-cancer type testing indicated the existence of shared genomic patterns across various cancers at the epitranscriptome level. A pan-cancer model was subsequently developed to identify these shared patterns that could not be observed in a single cancer type. Our analysis uncovered, for the first time, a common epitranscriptome signature shared across multiple cancer types, particularly associated with RNA hybridization process and aberrant splicing. This highlights the importance of a comprehensive understanding of the pan-cancer epitranscriptome and holding potential implications in the development of RNA methylation-based therapeutics for various cancers.

Essentials of genomics in nursing undergraduate education: A discussion paper

AimTo map the 2021 American Association of Colleges of Nursing Essentials to the American Nurses Association Essentials of Genomic Nursing for all nurses and provide resources for nursing faculty to support the seamless integration of genomics into existing undergraduate curricula. BackgroundSince the completion of the Human Genome Project in 2003, rapid advancements in genomic science leading to practical applications of genomics have revolutionized all areas of healthcare. Nursing is built on foundational life sciences, including genomics. As the largest segment of the healthcare workforce, who spend the most time with patients and families, nurses play a critical role in healthcare teams integrating genomic knowledge into patient care to improve health and well-being. Consequently, nurses must be equipped with foundational genomic knowledge and skills during their undergraduate education. However, there is wide variability in whether and how nursing programs have incorporated genomics into their curricula. Additionally, nursing faculty may have limited knowledge of foundational genomic concepts and lack confidence in teaching genomics. DesignDiscussion paper MethodsWe aligned domains from the American Association of Colleges of Nursing Essentials and American Nurses Association Essentials of Genomic Nursing. ResultsA map illustrating alignment in multiple areas, which provide examples of ways to integrate genomics into existing nursing curricula. ConclusionAlthough based on domains developed in the United States, the map, curricular resources, example learning outcomes, and clinical vignettes can be used by nursing faculty globally to prepare future nurses who are competent in providing genomics-informed nursing care on entry-to-practice.

Unveiling pharmacogenomics: insights from Portuguese pharmacists on quaternary prevention

Abstract Background Public health genomics recognises the potential of genomic knowledge for enhancing population health. Adverse drug reactions (ADR) and lack of efficacy have significant clinical and economic burdens, which can be mitigated by pharmacogenomics (PGx) testing. Pharmacists can play a vital role in facilitating the implementation of PGx into routine clinical care. This will promote quaternary prevention, to protect individuals from medical intervention that can cause more harm than good. Objectives To assess attitudes, opinions, expectations, practices, and concerns of Portuguese pharmacists regarding PGx implementation. Methods An observational cross-sectional web-based survey was developed based on literature review, adapted to the national context, and validated in a focus group. The target population were adults residing in Portugal with a degree in Pharmaceutical Sciences or equivalent, with convenience sampling. Descriptive statistics were performed. Results From 303 participants, 98% believe that PGx is an important area of pharmaceutical sciences and 97% indicate that PGx should be included in continuing education. Almost all (99%) anticipate that PGx implementation will prevent the administration of ineffective drugs and inappropriate doses, 98% expect PGx will reduce ADR. Major concerns are related with direct-to-consumer sale of PGx tests via internet (78%) and unauthorized access to test results (91%). Currently, 25% are familiar with reliable sources of information on PGx, but only 11% feel qualified to recommend PGx testing, and 10% have analysed PGx reports. Conclusions There are positive opinions and expectations regarding the potential benefits of PGx tests. However, there are regulatory concerns and lack of readiness for immediate application. Pharmacists express interest in learning more about PGx, highlighting the need for continuous education and training to integrate it effectively into routine pharmaceutical practice. Key messages • Pharmacists recognize the benefits of PGx implementation for quaternary prevention. • Regulatory concerns and readiness gaps in PGx emphasise a need for training and life-long education of pharmacists.

AKT and the Hallmarks of Cancer.

Nearly a quarter century ago, Hanahan and Weinberg conceived six unifying principles explaining how normal cells transform into malignant tumors. Their provisional set of biological capabilities acquired during tumor development  cancer hallmarks  would evolve to fourteen tenets as knowledge of cancer genomes, molecular mechanisms, and the tumor microenvironment expanded, most recently adding four emerging enabling characteristics: phenotypic plasticity, epigenetic reprogramming, polymorphic microbiomes, and senescent cells. AKT kinases are critical signaling molecules that regulate cellular physiology upon receptor tyrosine kinases and phosphatidylinositol 3-kinase activation. The complex branching of the AKT signaling network involves several critical downstream nodes that significantly magnify its functional impact, such that nearly every organ system and cell in the body may be affected by AKT activity. Conversely, tumor intrinsic dysregulation of AKT can have numerous adverse cellular and pathological ramifications, particularly in oncogenesis, as multiple tumor suppressors and oncogenic proteins regulate AKT signaling. Herein, we review the mounting evidence implicating the AKT pathway in the aggregate of currently recognized hallmarks of cancer underlying the complexities of human malignant diseases. The challenges, recent successes, and likely areas for exciting future advances in targeting this complex pathway are also discussed.

CardioGraph: a platform to study variations associated with familiar cardiopathies

BackgroundFamiliar cardiopathies are genetic disorders that affect the heart. Cardiologists face a significant problem when treating patients suffering from these disorders: most DNA variations are novel (i.e., they have not been classified before). To facilitate the analysis of novel variations, we present CardioGraph, a platform specially designed to support the analysis of novel variations and help determine whether they are relevant for diagnosis. To do this, CardioGraph identifies and annotates the consequence of variations and provides contextual information regarding which heart structures, pathways, and biological processes are potentially affected by those variations.MethodsWe conducted our work through three steps. First, we define a data model to support the representation of the heterogeneous information. Second, we instantiate this data model to integrate and represent all the genomics knowledge available for familiar cardiopathies. In this step, we consider genomic data sources and the scientific literature. Third, the design and implementation of the CardioGraph platform. A three-tier structure was used: the database, the backend, and the frontend.ResultsThree main results were obtained: the data model, the knowledge base generated with the instantiation of the data model, and the platform itself. The platform code has been included as supplemental material in this manuscript. Besides, an instance is publicly available in the following link: https://genomics-hub.pros.dsic.upv.es:3090.ConclusionCardioGraph is a platform that supports the analysis of novel variations. Future work will expand the body of knowledge about familiar cardiopathies and include new information about hotspots, functional studies, and previously reported variations.

Genome-wide association study of salt tolerance at the seed germination stage in lettuce.

Developing lettuce varieties with salt tolerance at the seed germination stage is essential since lettuce seeds are planted half an inch deep in soil where salt levels are often highest in the salinity-affected growing regions. Greater knowledge of genetics and genomics of salt tolerance in lettuce will facilitate breeding of improved lettuce varieties with salt tolerance. Accordingly, we conducted a genome-wide association study (GWAS) in lettuce to identify marker-trait association for salt tolerance at the seed germination stage. The study involved 445 diverse lettuce accessions and 56,820 single nucleotide polymorphism (SNP) markers obtained through genotype-by-sequencing technology using lettuce reference genome version v8. GWAS using two single-locus and three multi-locus models for germination rate (GR) under salinity stress, 5 days post seeding (GR5d_S) and a salinity susceptibility index (SSI) based on GR under salinity stress and control conditions, 5 days post seeding (SSI_GR5d) revealed 10 significant SNPs on lettuce chromosomes 2, 4, and 7. The 10 SNPs were associated with five novel QTLs for salt tolerance in lettuce, explaining phenotyping variations of 5.85%, 4.38%, 4.26%, 3.77%, and 1.80%, indicating the quantitative nature of these two salt tolerance-related traits. Using the basic local alignment search tool (BLAST) within 100 Kb upstream and downstream of each of the 10 SNPs, we identified 25 salt tolerance-related putative candidate genes including four genes encoding for major transcription factors. The 10 significant salt tolerance-related SNPs and the 25 candidate genes identified in the current study will be a valuable resource for molecular marker development and marker-assisted selection for breeding lettuce varieties with improved salt tolerance at the seed germination stage.

Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure.

Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. The constriction and dilation of arterioles regulate tissue perfusion and are primary determinants of systemic blood pressure (BP). Abnormalities in arterioles are central to the development of major diseases such as hypertension, stroke, and microvascular complications of diabetes. Despite the broad and essential role of arterioles in physiology and disease, current knowledge of the functional genomics of arterioles is largely absent, partly because it is challenging to obtain and analyze human arteriole samples. Here, we report extensive maps of chromatin interactions, single-cell expression, and other molecular features in human arterioles and uncover new mechanisms linking human genetic variants to gene expression in vascular cells and the development of hypertension. Compared to large arteries, arterioles exhibited a higher proportion of pericytes which were strongly associated with BP traits. BP-associated single nucleotide polymorphisms (SNPs) were enriched in chromatin interaction regions in arterioles, particularly through enhancer SNP-promoter interactions, which were further linked to gene expression specificity across tissue components and cell types. Using genomic editing in animal models and human induced pluripotent stem cells, we discovered novel mechanisms linking BP-associated noncoding SNP rs1882961 to gene expression through long-range chromatin contacts and revealed remarkable effects of a 4-bp noncoding genomic segment on hypertension in vivo. We anticipate that our rich data and findings will advance the study of the numerous diseases involving arterioles. Moreover, our approach of integrating chromatin interaction mapping in trait-relevant tissues with SNP analysis and in vivo and in vitro genome editing can be applied broadly to bridge the critical gap between genetic discoveries and physiological understanding.

The Clinical Genome Resource (ClinGen): Advancing genomic knowledge through global curation.

The Clinical Genome Resource (ClinGen) is a National Institutes of Health-funded program founded 10 years ago that defines the clinical relevance of genes and variants for medical and research use. ClinGen working groups develop standards for data sharing and curating genomic knowledge. Expert panels, with >2500 active members from 67 countries, curate the validity of monogenic disease relationships, pathogenicity of genetic variation, dosage sensitivity of genes, and actionability of gene-disease interventions using ClinGen standards, infrastructure, and curation interfaces. Results are available on clinicalgenome.org and classified variants are also submitted to ClinVar, a publicly available database hosted by the National Institutes of Health. As of January 2024, over 2700 genes have been curated (2420 gene-disease relationships for validity, 1557 genes for dosage sensitivity, and 447 gene-condition pairs for actionability), and 5161 unique variants have been classified for pathogenicity. New efforts are underway in somatic cancer, complex disease and pharmacogenomics, and a systematic approach to addressing justice, equity, diversity, and inclusion. ClinGen's knowledge can be used to build evidence-based genetic testing panels, interpret copy-number variation, resolve discrepancies in variant classification, guide disclosure of genomic findings to patients, and assess new predictive algorithms. To get involved in ClinGen activities go to https://www.clinicalgenome.org/start.

From fibers, to flowering, to metabolites: unlocking hemp (Cannabis sativa L.) potential with the guidance of novel discoveries and tools.

Cannabis sativa L. is an ancient crop whose agricultural adoption has been interrupted to prevent the use of marijuana as psychoactive drug. Nevertheless, hemp - the Cannabis sativa type with low concentrations of intoxicating Δ9-tetrahydrocannabinoid - is experiencing resurged interest thanks to loosened cultivation restrictions and its potential as multipurpose bio-based crop. In fact, hemp has valuable applications, including production of medicines from its non-intoxicating cannabinoids, food, medical, and industrial uses of its seed oil rich in poly-unsaturated fatty acids, and production of fibers for textiles and industry from its stems. Recently, several hemp genomic and genetic resources have been developed, allowing for a significant expansion of the genetic knowledge on major hemp traits, as cannabinoids, oil, and fibers synthesis, and regulation of flowering and sex determination. Still, hemp is an under-improved crop, whose advancement will depend on the ability to expand and collectively use the novel resources available in light of the fast advancements in bioinformatics and plant phenotyping technologies. This review discusses on the current genetic and genomic knowledge on the most important hemp traits, and provides a perspective on how to further expand such knowledge and tackle hemp improvement with the most up-to-date tools for plant and hemp research.

GNN4DM: a graph neural network-based method to identify overlapping functional disease modules.

Identifying disease modules within molecular interaction networks is an essential exploratory step in computational biology, offering insights into disease mechanisms and potential therapeutic targets. Traditional methods often struggle with the inherent complexity and overlapping nature of biological networks, and they are limited in effectively leveraging the vast amount of available genomic data and biological knowledge. This limitation underscores the need for more effective, automated approaches to integrate these rich data sources. In this work, we propose GNN4DM, a novel graph neural network-based structured model that automates the discovery of overlapping functional disease modules. GNN4DM effectively integrates network topology with genomic data to learn the representations of the genes corresponding to functional modules and align these with known biological pathways for enhanced interpretability. Following the DREAM benchmark evaluation setting and extending with three independent data sources (GWAS Atlas, FinnGen, and DisGeNET), we show that GNN4DM performs better than several state-of-the-art methods in detecting biologically meaningful modules. Moreover, we demonstrate the method's applicability by discovering two novel multimorbidity modules significantly enriched across a diverse range of seemingly unrelated diseases. Source code, all training data, and all identified disease modules are freely available for download at https://github.com/gezsi/gnn4dm. GNN4DM was implemented in Python.

Project GIVE: using a virtual genetics service platform to reduce health inequities and improve access to genomic care in an underserved region of Texas

BackgroundThe utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of improving pediatric health outcomes. We describe our experience of establishing a virtual pediatric genomic service in this region to expeditiously identify, recruit, and evaluate pediatric patients with undiagnosed diseases.MethodsWe have utilized an innovative electronic health record (EHR) agnostic virtual telehealth and educational platform called Consultagene to receive referrals from healthcare providers in the RGV. Using this portal, genetic services, including virtual evaluation and genome sequencing (GS), are being delivered to children with rare diseases. The study has also integrated effective methods to involve and educate community providers through in-person meetings and Continuing Professional Education (CPE) events.ResultsThe recruitment efforts have proven highly successful with the utilization of Consultagene in this medically underserved region. The project’s ongoing engagement efforts with local healthcare providers have resulted in progressively more referrals to the study over time, thus improving inclusion and access to genomic care in the RGV. Additionally, the curated CPE content has been well received by healthcare providers in the region.ConclusionsProject GIVE study has allowed advanced genetic evaluation and delivery of GS through the virtual Consultagene portal, effectively circumventing the recognized socioeconomic and logistical barriers to accessing genetic services within this border community.

A video intervention to improve patient understanding of tumor genomic testing in patients with cancer.

Tumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact of a concise 4 min video for patient education prior to TGT. Based on a quality improvement cycle, an animated video was created to be applicable to any cancer type, incorporating culturally diverse images, available in English and Spanish. Patients undergoing standard-of-care TGT were enrolled at a tertiary academic institution and completed survey instruments prior to video viewing (T1) and immediately post-viewing (T2). Instruments included: (1) 10-question objective genomic knowledge; (2) 10-question video message-specific knowledge; (3) 11-question Trust in Provider; (4) attitudes regarding TGT. A total of 150 participants were enrolled. For the primary objective, there was a significant increase in video message-specific knowledge (median 10 point increase; p < 0.0001) with no significant change in genomic knowledge/understanding (p = 0.89) or trust in physician/provider (p = 0.59). Results for five questions significantly improved, including the likelihood of TGT impact on treatment decision, incidental germline findings, and cost of testing. Improvement in video message-specific knowledge was consistent across demographic groups, including age, income, and education. A concise, 3-4 min, broadly applicable video incorporating culturally diverse images administered prior to TGT significantly improved video message-specific knowledge across all demographic groups. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.

Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.

Pediatric diffuse midline gliomas (DMG) with altered H3-K27M are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still poor. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer (TIM-3 Apt) as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in 2 pediatric DMG orthotopic murine models. Interestingly, TIM-3 Apt administration increased the number of myeloid populations and the proinflammatory CD8-to-Tregs ratios in the tumor microenvironment as compared with nontreated groups after radiotherapy. Importantly, the depletion of T cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.

Genetic diversity of a Silybum marianum (L.) Gaertn. germplasm collection revealed by DNA Diversity Array Technology (DArTseq).

Silybum marianum (L.) Gaertn. is a multipurpose crop native to the Mediterranean and middle east regions and mainly known for the hepatoprotective properties of fruit-derived silymarin. Despite growing interest in milk thistle as a versatile crop with medicinal value, its potential in agroindustry is hindered by incomplete domestication and limited genomic knowledge, impeding the development of competitive breeding programs. The present study aimed to evaluate genetic diversity in a panel of S. marianum accessions (n = 31), previously characterized for morphological and phytochemical traits, using 5,178 polymorphic DArTseq SNP markers. The genetic structure investigated using both parametric and non-parametric approaches (e.g. PCA, AWclust, Admixture), revealed three distinctive groups reflecting geographical origins. Indeed, Pop1 grouped accessions from Central Europe and UK, Pop3 consisted mainly of accessions of Italian origin, and Pop2 included accessions from different geographical areas. Interestingly, Italian genotypes showed a divergent phenotypic distribution, particularly in fruit oleic and linoleic acid content, compared to the other two groups. Genetic differentiation among the three groups, investigated by computing pairwise fixation index (FST), confirmed a greater differentiation of Pop3 compared to other subpopulations, also based on other diversity indices (e.g. private alleles, heterozygosity). Finally, 22 markers were declared as putatively under natural selection, of which seven significantly affected some important phenotypic traits such as oleic, arachidonic, behenic and linoleic acid content. These findings suggest that these markers, and overall, the seven SNP markers identified within Pop3, could be exploited in specific breeding programs, potentially aimed at diversifying the use of milk thistle. Indeed, incorporating genetic material from Pop3 haplotypes carrying the selected loci into milk thistle breeding populations might be the basis for developing milk thistle lines with higher levels of oleic, arachidonic, and behenic acids, and lower levels of linoleic acid, paving new avenues for enhancing the nutritional and agronomic characteristics of milk thistle.