Corrigendum: Validation of the GALAD model and establishment of a new model for HCC detection in Chinese patients.

[This corrects the article DOI: 10.3389/fonc.2022.1037742.].

Validation of the hepatocellular carcinoma early detection screening algorithm Doylestown and aMAP in a cohort of Chinese with cirrhosis.

BACKGROUND: Previous studies have developed some blood-based biomarker algorithms such as the Doylestown algorithm and aMAP score to improve the detection of Hepatocellular carcinoma (HCC). However, no one has studied the application of the Doylestown algorithm in the Chinese. Meanwhile, which of these two screening models is more suitable for people with liver cirrhosis remains to be investigated. METHODS: In this study, HCC surveillance was performed by radiographic imaging and testing for tumor markers every 6 months from August 21, 2018, to January 12, 2021. We conducted a retrospective study of 742 liver cirrhosis patients, and among them, 20 developed HCC during follow-up. Samples from these patients at three follow-up time points were tested to evaluate alpha-fetoprotein (AFP), the Doylestown algorithm, and aMAP score. RESULTS: Overall, 521 liver cirrhosis patients underwent semiannual longitudinal follow-up three times. Five patients were diagnosed with HCC within 0-6 months of the third follow-up. We found that for these liver cirrhosis patients, the Doylestown algorithm had the highest accuracy for HCC detection, with areas under the receiver operating characteristic curve (AUCs) of 0.763, 0.801, and 0.867 for follow-ups 1-3, respectively. Compared with AFP at 20 ng/ml, the Doylestown algorithm increased biomarker performance by 7.4%, 21%, and 13% for follow-ups 1-3, respectively. CONCLUSIONS: Our findings show that the Doylestown algorithm performance appeared to be optimal for HCC early screening in the Chinese cirrhotic population when compared with the aMAP score and AFP at 20 ng/ml.

Validation of the GALAD model and establishment of a new model for HCC detection in Chinese patients.

Background: GALAD model is a statistical model used to estimate the possibility of hepatocellular carcinoma (HCC) in patients with chronic liver disease. Many studies with other ethnic populations have shown that it has high sensitivity and specificity. However, whether this model can be used for Chinese patients remains to be determined. Our study was conducted to verify the performance of GALAD model in a Chinese cohort and construct a new model that is more appropriately for Chinese populations. Methods: There are total 512 patients enrolled in the study, which can be divided into training set and validation set. 80 patients with primary liver cancer, 139 patients with chronic liver disease and 87 healthy people were included in the training set. Through the ROC(receiver operating characteristic) curve analysis, the recognition performance of GALAD model for liver cancer was evaluated, and the GAADPB model was established by logistic regression, including gender, age, AFP, DCP, total protein, and total bilirubin. The validation set (75 HCC patients and 130 CLD patients) was used to evaluate the performance of the GAADPB model. Result: The GALAD and GAADPB achieved excellent performance (area under the receiver operating characteristic curve [AUC], 0.925, 0.945), and were better than GAAP, Doylestown, BALAD-2, aMAP, AFP, AFP-L3%, DCP and combined detection of AFP, AFP-L3 and DCP (AUCs: 0.894, 0.870, 0.648, 0.545, 0.879, 0.782, 0.820 and 0.911) for detecting HCC from CLD in the training set. As for early stage of HCC (BCLC 0/A), GAADPB had the best sensitivity compared to GALAD, ADP and DCP (56.3%, 53.1%, 40.6%, 50.0%). GAADPB had better performance than GALAD in the test set, AUC (0.896 vs 0.888). Conclusions: The new GAADPB model was powerful and stable, with better performance than the GALAD and other models, and it also was promising in the area of HCC prognosis prediction. Further study on the real-world HCC patients in China are needed.

Chromosome-scale assembly and high-density genetic map of the yellow drum, Nibea albiflora.

The yellow drum (Nibea albiflora) is an economically important sciaenid fish in East Asian countries. In this study, we sequenced and assembled a near-complete gynogenetic yellow drum genome. We generated 45.63 Gb of Illumina short-reads and 80.27 Gb of PacBio long-reads and assembled them into a 628.01-Mb genome with a contig N50 of 4.42 Mb. Twenty-four chromosomes with a scaffold N50 of 26.73 Mb were obtained using the Hi-C analysis. We predicted a set of 27,069 protein-coding genes, of which 1,581 and 2,583 were expanded and contracted gene families, respectively. The most expanded genes were categorised into the protein binding, zinc-ion binding and ATP binding functional pathways. We built a high-density genetic linkage map that spanned 4,300.2 cM with 24 linkage groups and a resolution of 0.69 cM. The high-quality reference genome and annotated profiles that we produced will not only increase our understanding of the genetic architecture of economic traits in the yellow drum, but also help us explore the evolution and unique biological characteristics of sciaenid fishes.

Resequencing of 296 cultivated and wild lotus accessions unravels its evolution and breeding history.

Lotus (family: Nelumbonaceae) are perennial aquatic plants that represent one of the most ancient basal dicots. In the present study, we resequenced 296 lotus accessions from various geographical locations and germplasms to explore their genomic diversity and population structure. This germplasm set consisted of four accessions of American wild lotus and 292 accessions of Asian lotus, which were divided into four subgroups: wild, rhizome, flower and seed. Total single nucleotide polymorphisms (SNPs) suggested that the wild lotus had the highest variant number (7 191 010). Population structure and genome diversity analysis indicated that the American wild lotus demonstrated a distant genetic relationship with the Asian lotus. Furthermore, the seed and rhizome lotus groups had not originated from a single source but rather had a more complex multisource origin. Besides that, the seed lotus showed higher genetic diversity, which might have been due to the gene flow from the flower lotus to seed lotus by artificial crossing, and the rhizome lotus showed a much lower genetic diversity than the other groups. The present study provides SNP markers for lotus genomic diversity analysis, which will be useful for guiding lotus breeding.

Construction of a high-density genetic map with whole genome sequencing in Nicotiana tabacum L.

Tobacco (Nicotiana tabacum L.) is an essential commercial crop and an ideal model plant for biological mechanism studies. As an allopolyploid species, tobacco harbors a massive and complex genome, which makes the application of molecular markers complicated and challenging. In our study, we performed whole-genome sequencing of an intraspecific recombinant inbred line (RIL) population, a F1 generation and their parents. With the Nicotiana tabacum (K326 cultivar) genome as reference, a total of 45,081 markers were characterized to construct the genetic map, which spanned a genetic distance of 3486.78 cM. Evaluation of a two-dimensional heat map proved the high quality of the genetic map. We utilized these markers to anchor scaffolds and analyzed the ancestral genome origin of linkage groups (LGs). Furthermore, such a high-density genetic map will be applied for quantitative trait locus (QTL) detection, gene localization, genome-wide association studies (GWAS), and marker-assisted breeding in tobacco.

Origin and evolution of qingke barley in Tibet.

Tibetan barley (Hordeum vulgare L., qingke) is the principal cereal cultivated on the Tibetan Plateau for at least 3,500 years, but its origin and domestication remain unclear. Here, based on deep-coverage whole-genome and published exome-capture resequencing data for a total of 437 accessions, we show that contemporary qingke is derived from eastern domesticated barley and it is introduced to southern Tibet most likely via north Pakistan, India, and Nepal between 4,500 and 3,500 years ago. The low genetic diversity of qingke suggests Tibet can be excluded as a center of origin or domestication for barley. The rapid decrease in genetic diversity from eastern domesticated barley to qingke can be explained by a founder effect from 4,500 to 2,000 years ago. The haplotypes of the five key domestication genes of barley support a feral or hybridization origin for Tibetan weedy barley and reject the hypothesis of native Tibetan wild barley.

Simple, Low-Cost Fabrication of Highly Uniform and Reproducible SERS Substrates Composed of Ag⁻Pt Nanoparticles.

Ag⁻Pt nanoparticles, grafted on Ge wafer, were synthesized by the galvanic replacement reaction based on their different potentials. Detailed characterization through scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDS) and X-ray photo-elelctron spectroscopy (XPS) proved that Ag⁻Pt nanoparticles are composed of large Ag nanoparticles and many small Pt nanoparticles instead of an Ag⁻Pt alloy. When applied as surface-enhanced Raman scattering (SERS) substrates to detect Rhodamine 6G (1 × 10-8 M) or Crystal violet (1 × 10-7 M) aqueous solution in the line mapping mode, all of the obtained relative standard deviation (RSD) values of the major characteristic peak intensities, calculated from the SERS spectra of 100 serial spots, were less than 10%. The fabrication process of the SERS substrate has excellent uniformity and reproducibility and is simple, low-cost and time-saving, which will benefit studies on the platinum-catalyzed reaction mechanisms in situ and widen the practical application of SERS.

Draft genome sequence of ramie, Boehmeria nivea (L.) Gaudich.

Ramie, Boehmeria nivea (L.) Gaudich, family Urticaceae, is a plant native to eastern Asia, and one of the world's oldest fibre crops. It is also used as animal feed and for the phytoremediation of heavy metal-contaminated farmlands. Thus, the genome sequence of ramie was determined to explore the molecular basis of its fibre quality, protein content and phytoremediation. For further understanding ramie genome, different paired-end and mate-pair libraries were combined to generate 134.31 Gb of raw DNA sequences using the Illumina whole-genome shotgun sequencing approach. The highly heterozygous B. nivea genome was assembled using the Platanus Genome Assembler, which is an effective tool for the assembly of highly heterozygous genome sequences. The final length of the draft genome of this species was approximately 341.9 Mb (contig N50 = 22.62 kb, scaffold N50 = 1,126.36 kb). Based on ramie genome annotations, 30,237 protein-coding genes were predicted, and the repetitive element content was 46.3%. The completeness of the final assembly was evaluated by benchmarking universal single-copy orthologous genes (BUSCO); 90.5% of the 1,440 expected embryophytic genes were identified as complete, and 4.9% were identified as fragmented. Phylogenetic analysis based on single-copy gene families and one-to-one orthologous genes placed ramie with mulberry and cannabis, within the clade of urticalean rosids. Genome information of ramie will be a valuable resource for the conservation of endangered Boehmeria species and for future studies on the biogeography and characteristic evolution of members of Urticaceae.