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Abstract Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm‐level (1p/19q codeletion, +7/−10 signature) and gene‐level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost‐effectiveness and versatility. However, the parallel detection of glioma‐associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model‐based approach to classify the CNV status of glioma‐associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model‐based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma‐associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm‐level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma‐associated markers in parallel.

BackgroundNiraparib, a poly ADP-ribose polymerase inhibitors (PARPi), has been widely applied in the intervention of epithelial ovarian, fallopian tube, or primary peritoneal cancer. Nevertheless, as of the present moment, there are limited instances demonstrating favorable outcomes stemming from niraparib therapy in patients with clear cell renal cell carcinoma (ccRCC).Case presentationHere, we report a case of a 50-year-old patient with ccRCC who subsequently developed distant metastasis. The patient received monotherapy with pazopanib and combination therapy with axitinib and tislelizumab, demonstrating limited efficacy. Liquid biopsy revealed missense mutations in the CDK12 and RAD51C of the homologous recombination repair (HRR) pathway, suggesting potential sensitivity to PARPi. Following niraparib treatment, the patient’s condition improved, with no significant side effects.ConclusionIn summary, patients with ccRCC harboring HRR pathway gene mutation may potentially benefit from niraparib. This will present more options for ccRCC patients with limited response to conventional treatments.

Flag-leaf-related traits including length (FLL), width (FLW), area (FLA), thickness (FLT), and volume (FLV) of flag leaves are the most important determinants of plant architecture and yield in wheat. Understanding the genetic basis of these traits could accelerate the breeding of high yield wheat varieties. In this study, we constructed a doubled haploid (DH) population and analyzed flag-leaf-related traits in five experimental locations/years using the wheat 90K single-nucleotide polymorphism array. It’s worth noting that a novel method was used to measure FLT and FLV easily. Leaf thickness at two-thirds of the leaf length from tip to collar represented the average leaf thickness as measured with freehand sections and was used to calculate the leaf volume. In addition, flag-leaf-related traits showed positive correlations with yield related traits under two different water regimes. A total of 79 quantitative trait loci (QTL) controlling the five traits were detected among all chromosomes except 4D and 5A, explaining 3.09–14.52% of the phenotypic variation. Among them, 15 stable QTL were identified in more than three environments, including two major QTL for FLT, six for FLW, three for FLA, two for FLT and two for FLV. DH lines with positive alleles at both QTL regions had an average FLL (9.90%), FLW (32.87%), FLT (6.62%), FLA (18.47%), and FLV (20.87%) greater than lines with contrasting alleles. QFLT-2B, QFLV-2A, and QFLV-7D were co-located with yield-related traits. The 15 QTL were validated by tightly linked kompetitive allele specific PCR (KASP) markers in a recombinant inbred line (RIL) population derived from a different cross. QFLL-4A, QFLW-4B, QFLA-5D.1, QFLA-7A, QFLA-7D.1, QFLT-2B, QFLT-6A, QFLV-2A, and QFLV-7D are likely novel loci. These results provide a better understanding of the genetic basis underlying flag-leaf-related traits. Also, target regions for fine mapping and marker-assisted selection were identified and these will be valuable for breeding high yielding bread wheat.

Chlorophyll content of the flag leaf is an important trait for drought resistance in wheat under drought stress. Understanding the regulatory mechanism of flag leaf chlorophyll content could accelerate breeding for drought resistance. In this study, we constructed a recombinant inbred line (RIL) population from a cross of drought-sensitive variety DH118 and drought-resistant variety Jinmai 919, and analyzed the chlorophyll contents of flag leaves in six experimental locations/years using the Wheat90K single-nucleotide polymorphism array. A total of 29 quantitative trait loci (QTLs) controlling flag leaf chlorophyll were detected with contributions to phenotypic variation ranging from 4.67 to 23.25%. Twelve QTLs were detected under irrigated conditions and 18 were detected under dryland (drought) conditions. Most of the QTLs detected under the different water regimes were different. Four major QTLs (Qchl.saw-3B.2, Qchl.saw-5A.2, Qchl.saw-5A.3, and Qchl.saw-5B.2) were detected in the RIL population. Qchl.saw-3B.2, possibly more suitable for marker-assisted selection of genotypes adapted to irrigated conditions, was validated by a tightly linked kompetitive allele specific PCR (KASP) marker in a doubled haploid population derived from a different cross. Qchl.saw-5A.3, a novel stably expressed QTL, was detected in the dryland environments and explained up to 23.25% of the phenotypic variation, and has potential for marker-assisted breeding of genotypes adapted to dryland conditions. The stable and major QTLs identified here add valuable information for understanding the genetic mechanism underlying chlorophyll content and provide a basis for molecular marker–assisted breeding.

Plant epidermal wax helps protect plants from adverse environmental conditions, maintains the function of tissues and organs, and ensures normal plant development. However, the constituents of epidermal wax and the regulatory mechanism of their biosynthesis in wheat have not been fully understood. Wheat varieties with different wax content, Jinmai47 and Jinmai84, were selected to comparatively analyze their waxy components and genetic characteristics, using a combination of lipidomic, transcriptomic, and BSA-Wheat 660K chip analysis. Through lipidomic analysis, 1287 lipid molecules were identified representing 31 lipid subclasses. Among these, Diacylglycerols (DG), (O-acyl)-ω-hydroxy fatty acids (OAHFA), wax ester (WE), Triacylglycerols (TG), and Monoradylglycerols (MG) accounted for 96.4% of the total lipids in Jinmai84 and 94.5% in Jinmai47. DG, OAHFA, and WE were higher in Jinmai84 than in Jinmai47 with the content of OAHFA 2.88-fold greater and DG 1.66-fold greater. Transcriptome sequence and bioinformatics analysis revealed 63 differentially expressed genes related to wax biosynthesis. Differentially expressed genes (DEGs) were found to be involved with the OAHFA, DG, and MG of synthesis pathways, which enriched the wax metabolism pathway. Non-glaucous and glaucous bulks from a mapping population were used to identify single nucleotide polymorphisms (SNP) via 660K chip analysis. Two loci centered on chromosomes 2D and 4B were detected and the locus on 4B is likely novel. These data improve understanding of complex lipid metabolism for cuticular wax biosynthesis in wheat and lay the foundation for future detailed investigation of mechanisms regulating wax metabolism.

Walnut oil is an excellent source of essential fatty acids. Systematic evaluation of walnut lipids has significance for the development of the nutritional and functional value of walnut. Ultra-performance liquid chromatography/Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap HRMS) was used to characterize the lipids of walnut. A total of 525 lipids were detected and triacylglycerols (TG) (18:2/18:2/18:3) and diacylglycerols (DG) (18:2/18:2) were the main glycerolipids present. Essential fatty acids, such as linoleic acid and linolenic acid, were the main DG and TG fatty acid chains. Many types of phospholipids were observed with phosphatidic acid being present in the highest concentration (5.58%). Using a combination of metabolome and transcriptome analysis, the present study mapped the main lipid metabolism pathway in walnut. These results may provide a theoretical basis for further study and specific gene targets to enable the development of walnut with increased oil content and modified fatty acid composition.

The synonymous codons usage shows a characteristic pattern of preference in each organism. This codon usage bias is thought to have evolved for efficient protein synthesis. Synonymous codon usage was studied in genes of the hexaploid wheat Triticum aestivum (AABBDD) and its progenitor species, Triticum urartu (AA), Aegilops tauschii (DD), and Triticum turgidum (AABB). Triticum aestivum exhibited stronger usage bias for G/C-ending codons than did the three progenitor species, and this bias was especially higher compared to T. turgidum and Ae. tauschii. High GC content is a primary factor influencing codon usage in T. aestivum. Neutrality analysis showed a significant positive correlation (p