Systems Biology

TeloSearchLR: an algorithm to detect novel telomere repeat motifs using long sequencing reads

Tue, 2025-04-01 06:00

G3 (Bethesda). 2025 Apr 2:jkaf062. doi: 10.1093/g3journal/jkaf062. Online ahead of print.

ABSTRACT

Telomeres are eukaryotic chromosome end structures that guard against sequence loss and aberrant chromosome fusions. Telomeric repeat motifs (TRMs), the minimal repeating unit of a telomere, vary from species to species, with some evolutionary clades experiencing a rapid sequence divergence. To explore the full scope of this evolutionary divergence, many bioinformatic tools have been developed to infer novel TRMs using repetitive sequence search on short sequencing reads. However, novel telomeric motifs remain unidentified in up to half of the sequencing libraries assayed with these tools. A possible reason may be that short reads, derived from extensively sheared DNA, preserve little to no positional context of the repetitive sequences assayed. On the other hand, if a sequencing read is sufficiently long, telomeric sequences must appear at either end rather than in the middle. The TeloSearchLR algorithm relies on this to help identify novel TRMs on long reads, in many cases where short-read search tools have failed. In addition, we demonstrate that TeloSearchLR can reveal unusually long telomeric motifs not maintained by telomerase, and it can also be used to anchor terminal scaffolds in new genome assemblies.

PMID:40169380 | DOI:10.1093/g3journal/jkaf062

Categories: Literature Watch

Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection

Tue, 2025-04-01 06:00

Cell Host Microbe. 2025 Mar 25:S1931-3128(25)00088-5. doi: 10.1016/j.chom.2025.03.005. Online ahead of print.

ABSTRACT

Many eukaryotic viruses require membrane-bound compartments for replication, but no such organelles are known to be formed by prokaryotic viruses. Bacteriophages of the Chimalliviridae family sequester their genomes within a phage-generated organelle, the phage nucleus, which is enclosed by a lattice of the viral protein ChmA. We show that inhibiting phage nucleus formation arrests infections at an early stage in which the injected phage genome is enclosed within a membrane-bound early phage infection (EPI) vesicle. Early phage genes are expressed from the EPI vesicle, demonstrating its functionality as a prokaryotic, transcriptionally active, membrane-bound organelle. We also show that the phage nucleus is essential, with genome replication beginning after the injected DNA is transferred from the EPI vesicle to the phage nucleus. Our results show that Chimalliviridae require two sophisticated subcellular compartments of distinct compositions and functions that facilitate successive stages of the viral life cycle.

PMID:40168997 | DOI:10.1016/j.chom.2025.03.005

Categories: Literature Watch

Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria

Tue, 2025-04-01 06:00

Cell Host Microbe. 2025 Mar 25:S1931-3128(25)00091-5. doi: 10.1016/j.chom.2025.03.008. Online ahead of print.

ABSTRACT

Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole (PV) to help clear Plasmodium. Second, guanylate-binding protein (GBP) 1-mediated disruption of the PV activates the caspase-1 inflammasome, inducing pyroptosis to remove infected host cells. Remarkably, both human and mouse hepatocytes enlist these cell-autonomous immune programs to eliminate Plasmodium, with their pharmacologic or genetic inhibition leading to profound malarial susceptibility in vivo. In addition to identifying IFN-I-mediated cell-autonomous immune circuits controlling Plasmodium infection in the hepatocytes, our study also extends the understanding of how non-immune cells are integral to protective immunity against malaria.

PMID:40168996 | DOI:10.1016/j.chom.2025.03.008

Categories: Literature Watch

Perspectives on the role of "-Omics" in predicting response to immunotherapy

Tue, 2025-04-01 06:00

Eur J Cancer. 2025 Mar 30;220:115393. doi: 10.1016/j.ejca.2025.115393. Online ahead of print.

ABSTRACT

The annual Immuno-Oncology "Think Tank" held in October 2023 in Siena reviewed the rapidly evolving systems-biological approaches which are now providing a deeper understanding of tumor and tumor microenvironment heterogeneity. Based on this understanding opportunities for novel therapies may be identified to overcome resistance to immunotherapy. There is increasing evidence that malignant disease processes are not limited to purely intracellular or genetic events but constitute a dynamic interaction between the host and disease. Tumor responses are influenced by many host tissue determinants across different cellular compartments, which can now be investigated by high-throughput molecular profiling technologies, often labelled with a suffix "-omics". "Omics" together with ever increasing computational power, fast developments in machine learning, and high-resolution detection tools offer an unrivalled opportunity to connect high-dimensional data and create a holistic view of disease processes in cancer. This review describes advances in several state-of-the-art "-omics" approaches with perspectives on how these can be applied to the clinical development of new immunotherapeutic strategies and ultimately adopted in clinical practice.

PMID:40168935 | DOI:10.1016/j.ejca.2025.115393

Categories: Literature Watch

An agricultural triazole induces genomic instability and haploid cell formation in the human fungal pathogen Candida tropicalis

Tue, 2025-04-01 06:00

PLoS Biol. 2025 Apr 1;23(4):e3003062. doi: 10.1371/journal.pbio.3003062. eCollection 2025 Apr.

ABSTRACT

The human fungal pathogen Candida tropicalis is widely distributed in clinical and natural environments. It is known to be an obligate diploid organism with an incomplete and atypical sexual cycle. Azole-resistant C. tropicalis isolates have been observed with increasing prevalence in many countries in recent years. Here, we report that tebuconazole (TBZ), a triazole fungicide widely used in agriculture, can induce ploidy plasticity and the formation of haploid cells in C. tropicalis. The evolved C. tropicalis strains with ploidy variations exhibit a cross-resistance between TBZ and standard azoles used in clinical settings (such as fluconazole and voriconazole). Similar to its diploid cells, these newly discovered C. tropicalis haploid cells are capable of undergoing filamentation, white-opaque switching, and mating. However, compared to its diploid cells, these haploid C. tropicalis cells grow more slowly under in vitro culture conditions and are less virulent in a mouse model of systemic infection. Interestingly, flow cytometry analysis of a clinical strain with extremely low genome heterozygosity indicates the existence of natural C. tropicalis haploids. Discovery of this C. tropicalis haploid state sheds new light into the biology and genetic plasticity of C. tropicalis and could provide the framework for the development of new genetic tools in the field.

PMID:40168394 | DOI:10.1371/journal.pbio.3003062

Categories: Literature Watch

Signaling networks in cancer stromal senescent cells establish malignant microenvironment

Tue, 2025-04-01 06:00

Proc Natl Acad Sci U S A. 2025 Apr 8;122(14):e2412818122. doi: 10.1073/pnas.2412818122. Epub 2025 Apr 1.

ABSTRACT

The tumor microenvironment (TME) encompasses various cell types, blood and lymphatic vessels, and noncellular constituents like extracellular matrix (ECM) and cytokines. These intricate interactions between cellular and noncellular components contribute to the development of a malignant TME, such as immunosuppressive, desmoplastic, angiogenic conditions, and the formation of a niche for cancer stem cells, but there is limited understanding of the specific subtypes of stromal cells involved in this process. Here, we utilized p16-CreERT2-tdTomato mouse models to investigate the signaling networks established by senescent cancer stromal cells, contributing to the development of a malignant TME. In pancreatic ductal adenocarcinoma (PDAC) allograft models, these senescent cells were found to promote cancer fibrosis, enhance angiogenesis, and suppress cancer immune surveillance. Notably, the selective elimination of senescent cancer stromal cells improves the malignant TME, subsequently reducing tumor progression in PDAC. This highlights the antitumor efficacy of senolytic treatment alone and its synergistic effect when combined with conventional chemotherapy. Taken together, our findings suggest that the signaling crosstalk among senescent cancer stromal cells plays a key role in the progression of PDAC and may be a promising therapeutic target.

PMID:40168129 | DOI:10.1073/pnas.2412818122

Categories: Literature Watch

Chromosome-Level Genome Assembly of the Loach Goby Rhyacichthys aspro Offers Insights Into Gobioidei Evolution

Tue, 2025-04-01 06:00

Mol Ecol Resour. 2025 Apr 1:e14110. doi: 10.1111/1755-0998.14110. Online ahead of print.

ABSTRACT

The percomorph fish clade Gobioidei is a suborder that comprises over 2200 species distributed in nearly all aquatic habitats. To understand the genetics underlying their species diversification, we sequenced and annotated the genome of the loach goby, Rhyacichthys aspro, an early-diverging group, and compared it with nine additional Gobioidei species. Within Gobioidei, the loach goby possesses the smallest genome at 594 Mb, and a rise in species diversity from early-diverging to more recently diverged lineages is mirrored by enlarged genomes and a higher presence of transposable elements (TEs), particularly DNA transposons. These DNA transposons are enriched in genic and regulatory regions and their copy number increase is strongly correlated with substitution rate, suggesting that DNA repair after transposon excision/insertion leads to nearby mutations. Consequently, the proliferation of DNA transposons might be the crucial driver of Gobioidei diversification and adaptability. The loach goby genome also points to mechanisms of ecological adaptation. It contains relatively few genes for lateral line development but an overrepresentation of synaptic function genes, with genes putatively under selection linked to synapse organisation and calcium signalling, implicating a sensory system distinct from other Gobioidei species. We also see an overabundance of genes involved in neurocranium development and renal function, adaptations likely connected to its flat morphology suited for strong currents and an amphidromous life cycle. Comparative analyses with hill-stream loaches and the European eel reveal convergent adaptations in body shape and saltwater balance. These findings shed new light on the loach goby's survival mechanisms and the broader evolutionary trends within Gobioidei.

PMID:40168108 | DOI:10.1111/1755-0998.14110

Categories: Literature Watch

Inspecting Biological Deregulation, Putative Markers, and Therapeutic Targets for Neurodegenerative Diseases Through an Integrative Bioinformatics Analysis of the Human Cerebrospinal Fluid Proteome: A Tutorial

Tue, 2025-04-01 06:00

Methods Mol Biol. 2025;2914:275-302. doi: 10.1007/978-1-0716-4462-1_20.

ABSTRACT

Cerebrospinal fluid (CSF) is a source of valuable information concerning brain disorders. The technical advances of high throughput omics platforms to analyze body fluids can generate a huge amount of data, whose translation of the biological meaning can be a challenge. Several bioinformatics tools have emerged to help handle this data from a systems biology perspective. Herein, we describe a step-by-step tutorial for CSF proteome data analysis in the set of neurodegenerative diseases using: (i) ShinyGO webtool to perform functional enrichment analysis envisioning the characterization of the biological pathways and processes deregulated in neurodegenerative diseases including Alzheimer's and Parkinson's diseases; (ii) Cytoscape to map disease-specific proteins based on evidence from proteomics; (iii) DisGeNET to identify the proteins more strongly and more specifically associated with neurodegenerative diseases to date; (iv) STRING to identify putative therapeutic targets through a combined protein-protein interaction and network topological analyses. This step-by-step guide might help researchers to better characterize disease pathogenesis and to identify putative disease biomarkers and therapeutic targets.

PMID:40167925 | DOI:10.1007/978-1-0716-4462-1_20

Categories: Literature Watch

Correction: Metabolomic heterogeneity of ageing with ethnic diversity: a step closer to healthy ageing

Tue, 2025-04-01 06:00

Metabolomics. 2025 Apr 1;21(2):48. doi: 10.1007/s11306-025-02247-x.

NO ABSTRACT

PMID:40167843 | DOI:10.1007/s11306-025-02247-x

Categories: Literature Watch

Microbiota-dependent modulation of intestinal anti-inflammatory CD4<sup>+</sup> T cell responses

Tue, 2025-04-01 06:00

Semin Immunopathol. 2025 Apr 1;47(1):23. doi: 10.1007/s00281-025-01049-6.

ABSTRACT

Barrier organs such as the gastrointestinal tract, lungs, and skin are colonized by diverse microbial strains, including bacteria, viruses, and fungi. These microorganisms, collectively known as the commensal microbiota, play critical roles in maintaining health by defending against pathogens, metabolizing nutrients, and providing essential metabolites. In the gut, commensal-derived antigens are frequently sensed by the intestinal immune system. Maintaining tolerance toward these beneficial microbial species is crucial, as failure to do so can lead to chronic inflammatory conditions like inflammatory bowel disease (IBD) and can even affect systemic immune or metabolic health. The immune system carefully regulates responses to commensals through various mechanisms, including the induction of anti-inflammatory CD4⁺ T cell responses. Foxp3⁺ regulatory T cells (Foxp3+ Tregs) and Type 1 regulatory T cells (Tr1) play a major role in promoting tolerance, as both cell types can produce the anti-inflammatory cytokine IL-10. In addition to these regulatory T cells, effector T cell subsets, such as Th17 cells, also adopt anti-inflammatory functions within the intestine in response to the microbiota. This process of anti-inflammatory CD4+ T cell induction is heavily influenced by the microbiota and their metabolites. Microbial metabolites affect intestinal epithelial cells, promoting the secretion of anti-inflammatory mediators that create a tolerogenic environment. They also modulate intestinal dendritic cells (DCs) and macrophages, inducing a tolerogenic state, and can interact directly with T cells to drive anti-inflammatory CD4⁺ T cell functionality. The disrupted balance of these signals may result in chronic inflammation, with broader implications for systemic health. In this review, we highlight the intricate interplays between commensal microorganisms and the immune system in the gut. We discuss how the microbiota influences the differentiation of commensal-specific anti-inflammatory CD4⁺ T cells, such as Foxp3⁺ Tregs, Tr1 cells, and Th17 cells, and explore the mechanisms through which microbial metabolites modulate these processes. We further discuss the innate signals that prime and commit these cells to an anti-inflammatory fate.

PMID:40167791 | DOI:10.1007/s00281-025-01049-6

Categories: Literature Watch

Metabolic engineering of lipids for crop resilience and nutritional improvements towards sustainable agriculture

Tue, 2025-04-01 06:00

Funct Integr Genomics. 2025 Apr 1;25(1):78. doi: 10.1007/s10142-025-01588-z.

ABSTRACT

Metabolic engineering of lipids in crops presents a promising strategy to enhance resilience against environmental stressors while improving nutritional quality. By manipulating key enzymes in lipid metabolism, introducing novel genes, and utilizing genome editing technologies, researchers have improved crop tolerance to abiotic stresses such as drought, salinity, and extreme temperatures. Additionally, modified lipid pathways contribute to resistance against biotic stresses, including pathogen attacks and pest infestations. Engineering multiple stress-resistance traits through lipid metabolism offers a holistic approach to strengthening crop resilience amid changing environmental conditions. Beyond stress tolerance, lipid engineering enhances the nutritional profile of crops by increasing beneficial lipids such as omega-3 fatty acids, vitamins, and antioxidants. This dual approach not only improves crop yield and quality but also supports global food security by ensuring sustainable agricultural production. Integrating advanced biotechnological tools with a deeper understanding of lipid biology paves the way for developing resilient, nutrient-rich crops capable of withstanding climate change and feeding a growing population.

PMID:40167787 | DOI:10.1007/s10142-025-01588-z

Categories: Literature Watch

Histone Deacetylase 6 (HDAC6) in Ciliopathies: Emerging Insights and Therapeutic Implications

Tue, 2025-04-01 06:00

Adv Sci (Weinh). 2025 Apr 1:e2412921. doi: 10.1002/advs.202412921. Online ahead of print.

ABSTRACT

HDAC6 is integral to the regulation of primary cilia, which are specialized structures that serve as crucial signaling hubs for cellular communication and environmental response. These ciliary functions are essential for maintaining cellular homeostasis and orchestrating developmental processes. Dysregulation of HDAC6 activity is implicated in ciliopathies, a group of disorders characterized by defective ciliary structure or function, resulting in widespread organ involvement and significant morbidity. This review provides a comprehensive examination of the molecular dynamics of HDAC6 in the context of ciliogenesis and ciliopathies, emphasizing its dual role in the deacetylation of microtubules and regulation of the ciliary axoneme. Furthermore, HDAC6 interacts with key signaling molecules, modulating processes ranging from cell cycle regulation to inflammatory responses, which highlights its central role in cellular physiology and pathology. The therapeutic potential of HDAC6 inhibitors has been explored, with promising results in various disease models, including retinal and renal ciliopathies, highlighting their ability to restore normal ciliary function. This analysis not only underscores the critical importance of HDAC6 in maintaining ciliary integrity but also illustrates how targeting the HDAC6-cilia axis could provide a groundbreaking approach to treating these complex disorders. In doing so, this review sets the stage for future investigations into HDAC6-targeted therapies, potentially transforming the clinical management of ciliopathies and significantly improving patient outcomes.

PMID:40167251 | DOI:10.1002/advs.202412921

Categories: Literature Watch

Severe cognitive decline in long-term care is related to gut microbiome production of metabolites involved in neurotransmission, immunomodulation, and autophagy

Tue, 2025-04-01 06:00

J Gerontol A Biol Sci Med Sci. 2025 Mar 28:glaf053. doi: 10.1093/gerona/glaf053. Online ahead of print.

ABSTRACT

Ageing-associated cognitive decline affects more than half of those in long-term residential aged care. Emerging evidence suggests that gut microbiome-host interactions influence the effects of modifiable risk factors. We investigated the relationship between gut microbiome characteristics and severity of cognitive impairment CI in 159 residents of long-term aged care. Severe CI was associated with a significantly increased abundance of proinflammatory bacterial species, including Methanobrevibacter smithii and Alistipes finegoldii, and decreased relative abundance of beneficial bacterial clades. Severe CI was associated with increased microbial capacity for methanogenesis, and reduced capacity for synthesis of short-chain fatty acids, neurotransmitters glutamate and gamma-aminobutyric acid, and amino acids required for neuro-protective lysosomal activity. These relationships were independent of age, sex, antibiotic exposure, and diet. Our findings implicate multiple gut microbiome-brain pathways in ageing-associated cognitive decline, including inflammation, neurotransmission, and autophagy, and highlight the potential to predict and prevent cognitive decline through microbiome-targeted strategies.

PMID:40166866 | DOI:10.1093/gerona/glaf053

Categories: Literature Watch

Disease prediction by network information gain on a single sample basis

Tue, 2025-04-01 06:00

Fundam Res. 2023 Feb 19;5(1):215-227. doi: 10.1016/j.fmre.2023.01.009. eCollection 2025 Jan.

ABSTRACT

There are critical transition phenomena during the progression of many diseases. Such critical transitions are usually accompanied by catastrophic disease deterioration, and their prediction is of significant importance for disease prevention and treatment. However, predicting disease deterioration solely based on a single sample is a difficult problem. In this study, we presented the network information gain (NIG) method, for predicting the critical transitions or disease state based on network flow entropy from omics data of each individual. NIG can not only efficiently predict disease deteriorations but also detect their dynamic network biomarkers on an individual basis and further identify potential therapeutic targets. The numerical simulation demonstrates the effectiveness of NIG. Moreover, our method was validated by successfully predicting disease deteriorations and identifying their potential therapeutic targets from four real omics datasets, i.e., an influenza dataset and three cancer datasets.

PMID:40166114 | PMC:PMC11955047 | DOI:10.1016/j.fmre.2023.01.009

Categories: Literature Watch

The RNA m<sup>6</sup>A Methyltransferase PheMTA1 and PheMTA2 of Moso Bamboo Regulate Root Development and Resistance to Salt Stress in Plant

Tue, 2025-04-01 06:00

Plant Cell Environ. 2025 Mar 31. doi: 10.1111/pce.15494. Online ahead of print.

ABSTRACT

As the most prevalent RNA modification in eukaryotes, N6-methyladenosine (m6A) plays a crucial role in regulating various biological processes in plants, including embryonic development and flowering. However, the function of m6A RNA methyltransferase in moso bamboo remains poorly understood. In this study, we identified two m6A methyltransferases in moso bamboo, PheMTA1 and PheMTA2. Overexpression of PheMTA1 and PheMTA2 significantly promoted root development and enhanced salt tolerance in rice. Using the HyperTRIBE method, we fused PheMTA1 and PheMTA2 with ADARcdE488Q and introduced them into rice. RNA sequencing (RNA-seq) of the overexpressing rice identified the target RNAs bound by PheMTA1 and PheMTA2. PheMTA1 and PheMTA2 bind to OsATM3 and OsSF3B1, which were involved in the development of root and salt resistance. Finally, we revealed the effects of transcription or alternative splicing on resistance-related genes like OsRS33, OsPRR73, OsAPX2 and OsHAP2E, which are associated with the observed phenotype. In conclusion, our study demonstrates that the m6A methyltransferases PheMTA1 and PheMTA2 from moso bamboo are involved in root development and enhance plant resistance to salt stress.

PMID:40165397 | DOI:10.1111/pce.15494

Categories: Literature Watch

Assessing the utility of genomic selection to breed for durable Ascochyta blight resistance in chickpea

Tue, 2025-04-01 06:00

Plant Genome. 2025 Jun;18(2):e70023. doi: 10.1002/tpg2.70023.

ABSTRACT

Ascochyta blight (AB) is one of the most devastating fungal diseases of chickpea (Cicer arietinum L.). Conventional breeding has focused on exploiting and introgressing major genes (qualitative effect) to improve AB resistance in released varieties. However, such approaches are time-consuming and prone to the breakdown of disease resistance due to the fast evolution of AB pathogen. Genomic selection (GS) offers a promising alternative by predicting breeding values using genome-wide single nucleotide polymorphisms (SNPs), regardless of major or minor effects. To our knowledge, this is the first study to develop and implement GS to improve AB resistance in chickpea. Over 4 years, 2790 chickpea lines, representing a broad range of germplasm collections primarily sourced from the Australian Grains Genebank, were evaluated for AB disease response in the field and in an outdoor pot-based facility. Plants were genotyped with the Illumina multispecies pulse 30K SNP array, resulting in 23,239 high-quality SNPs distributed across the genome. Intermediate-to-high genomic prediction accuracies (0.40-0.90) were achieved across validation scenarios. Bayesian modeling identified six major QTL explaining 33% of the genetic variance for AB resistance, with the remaining variance explained by minor effect genes. Using genomic estimated breeding values (GEBVs), 462 lines of the 2790 lines were predicted to have higher resistance compared to the released check varieties, revealing the potential of further improvement of AB resistance for the industry. The desirable genomic prediction accuracy obtained in the study supports the applicability of GS to breed for AB resistance in chickpea.

PMID:40164996 | DOI:10.1002/tpg2.70023

Categories: Literature Watch

Differential Glutamatergic Inputs to Semilunar Granule Cells and Granule Cells Underscore Dentate Gyrus Projection Neuron Diversity

Mon, 2025-03-31 06:00

bioRxiv [Preprint]. 2025 Mar 15:2025.03.14.643192. doi: 10.1101/2025.03.14.643192.

ABSTRACT

Semilunar Granule Cells (SGCs) are sparse dentate gyrus projection neurons whose role in the dentate circuit, including pathway specific inputs, remains unknown. We report that SGCs receive more frequent spontaneous excitatory synaptic inputs than granule cells (GCs). Dual GC-SGC recordings identified that SGCs receive stronger medial entorhinal cortex and associational synaptic drive but lack short-term facilitation of lateral entorhinal cortex inputs observed in GCs. SGCs dendritic spine density in proximal and middle dendrites was greater than in GCs. However, the strength of commissural inputs and dendritic input integration, examined in passive morphometric simulations, were not different between cell types. Activity dependent labeling identified an overrepresentation of SGCs among neuronal ensembles in both mice trained in a spatial memory task and task naïve controls. The divergence of modality specific inputs to SGCs and GCs can enable parallel processing of information streams and expand the computational capacity of the dentate gyrus.

PMID:40161709 | PMC:PMC11952520 | DOI:10.1101/2025.03.14.643192

Categories: Literature Watch

Segger: Fast and accurate cell segmentation of imaging-based spatial transcriptomics data

Mon, 2025-03-31 06:00

bioRxiv [Preprint]. 2025 Mar 16:2025.03.14.643160. doi: 10.1101/2025.03.14.643160.

ABSTRACT

The accurate assignment of transcripts to their cells of origin remains the Achilles heel of imaging-based spatial transcriptomics, despite being critical for nearly all downstream analyses. Current cell segmentation methods are prone to over- and under-segmentation, misassign transcripts to cells, require manual intervention, and suffer from low sensitivity and scalability. We introduce segger, a versatile graph neural network based on a heterogeneous graph representation of individual transcripts and cells, that frames cell segmentation as a transcript-to-cell link prediction task and can leverage single-cell RNA-seq information to improve transcript assignments. On multiple Xenium dataset benchmarks, segger exhibits superior sensitivity and specificity, while requiring orders of magnitude less compute time than existing methods. The user-friendly open-source software implementation has extensive documentation (https://elihei2.github.io/segger_dev/), requires little manual intervention, integrates seamlessly into existing workflows, and enables atlas-scale applications.

PMID:40161614 | PMC:PMC11952575 | DOI:10.1101/2025.03.14.643160

Categories: Literature Watch

Development of a cost-effective high-throughput mid-density 5K genotyping assay for germplasm characterization and breeding in groundnut

Mon, 2025-03-31 06:00

Plant Genome. 2025 Jun;18(2):e70019. doi: 10.1002/tpg2.70019.

ABSTRACT

Groundnut (Arachis hypogaea L.), also known as peanut, is an allotetraploid legume crop composed of two different progenitor sub-genomes. This crop is an important source for food, feed, and confectioneries. Leveraging translational genomics research has expedited the precision and speed in making selections of progenies in several crops through either marker-assisted selection or genomic selection, including groundnut. The availability of foundational genomic resources such as reference genomes for diploid progenitors and cultivated tetraploids, offered substantial opportunities for genomic interventions, including the development of genotyping assays. Here, a cost-effective and high-throughput genotyping assay has been developed with 5,081 single nucleotide polymorphisms (SNPs) referred to as "mid-density assay." This multi-purpose assay includes 5,000 highly informative SNPs selected based on higher polymorphism information content (PIC) from our previously developed high-density "Axiom_Arachis" array containing 58,233 SNPs. Additionally 82 SNPs associated with five resilience and quality traits were included for marker-assisted selection. To test the utility of the mid-density genotyping (MDG) assay, 2,573 genotypes from distinct sets of breeding populations were genotyped with the 5,081 SNPs. PIC of the SNPs in the MDG ranged from 0.34 to 0.37 among diverse sets. The first three principal components collectively explained 82.08% of the variance among these genotypes. The mid-density assay demonstrated a proficient ability to distinguish between the genotypes, offering a high level of genome-wide nucleotide diversity. This assay holds promise for possible deployment in the identification of varietal seed mixtures, genetic purity within gene bank germplasms and seed systems, foreground and background selection in backcross breeding programs, genomic selection, and sparse trait mapping studies in groundnut.

PMID:40164965 | DOI:10.1002/tpg2.70019

Categories: Literature Watch

Sharing data from the Human Tumor Atlas Network through standards, infrastructure and community engagement

Mon, 2025-03-31 06:00

Nat Methods. 2025 Mar 31. doi: 10.1038/s41592-025-02643-0. Online ahead of print.

ABSTRACT

Data from the first phase of the Human Tumor Atlas Network (HTAN) are now available, comprising 8,425 biospecimens from 2,042 research participants profiled with more than 20 molecular assays. The data were generated to study the evolution from precancerous to advanced disease. The HTAN Data Coordinating Center (DCC) has enabled their dissemination and effective reuse. We describe the diverse datasets, how to access them, data standards, underlying infrastructure and governance approaches, and our methods to sustain community engagement. HTAN data can be accessed through the HTAN Portal, explored in visualization tools-including CellxGene, Minerva and cBioPortal-and analyzed in the cloud through the NCI Cancer Research Data Commons. Infrastructure was developed to enable data ingestion and dissemination through the Synapse platform. The HTAN DCC's flexible and modular approach to sharing complex cancer research data offers valuable insights to other data-coordination efforts and researchers looking to leverage HTAN data.

PMID:40164800 | DOI:10.1038/s41592-025-02643-0

Categories: Literature Watch

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