[Application of Deep Learning in Differential Diagnosis of Ameloblastoma and Odontogenic Keratocyst Based on Panoramic Radiographs].

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.

Age Estimation using Panoramic Radiographs by Transfer Learning.

OBJECTIVE: To assess the accuracy of transfer learning models for age estimation from panoramic photographs of permanent dentition of patients with an equal sex and age distribution and provide a new method of age estimation. METHODS: The panoramic photographs of 3000 patients with an equal sex and age distribution were divided into three groups: a training set (n = 2400), validation set (n = 300) and test set (n = 300). The ResNet, EffiecientNet, VggNet and DenseNet transfer learning models were trained with the training set. The models were subsequently tested using the data in the test set. The mean absolute errors were calculated and the different features extracted by the deep learning models in different age groups were visualixed. RESULTS: The mean absolute error (MAE) and root mean square error (RMSE) of the optimal transfer learning model EfficientNet-B5 in the test set were 2.83 and 4.59, respectively. The dentition, maxillary sinus, mandibular body and mandibular angle all played a role in age estimation. CONCLUSION: Transfer learning models can extract different features in different age groups and can be used for age estimation in panoramic radiographs.

Diagnostic efficacy of CBCT, MRI and CBCT-MRI fused images in determining anterior disc displacement and bone changes of temporomandibular joint.

OBJECTIVES: To evaluate the diagnostic efficacy of CBCT-MRI fused image for anterior disc displacement and bone changes of temporomandibular joint (TMJ), which are the main imaging manifestations of temporomandibular disorders (TMD). METHODS: Two hundred and thirty-one TMJs of 120 patients who were diagnosed with TMD were selected for the study. The anterior disc displacement, bone defect and bone hyperplasia evaluated by three experts were used as a reference standard. Three residents individually evaluated all the three sets of images, which were CBCT images, MRI images and CBCT-MRI fused images from individual CBCT and MRI images in a random order for the above-mentioned three imaging manifestations with a five-point scale. Each set of images was observed at least 1 week apart. A second evaluation was performed 4 weeks later. Intra- and interobserver agreements were assessed using the intraclass correlation coefficient (ICC). The areas under the ROC curves (AUCs) of the three image sets were compared with a Z test, and p < 0.05 was considered statistically significant. RESULTS: One hundred and forty-five cases were determined as anterior disc displacement, 84 cases as bone defect and 40 cases as bone hyperplasia. The intra- and interobserver agreements in the CBCT-MRI fused image set (0.76-0.91) were good to excellent, and the diagnostic accuracy for bone changes was significantly higher than that of MRI image set (p＜0.05). CONCLUSIONS: CBCT-MRI fused images can display the disc and surrounding bone structures simultaneously and significantly improve the observers' reliability and diagnostic accuracy, especially for inexperienced residents.

Diagnostic efficacy of CBCT, MRI, and CBCT-MRI fused images in distinguishing articular disc calcification from loose body of temporomandibular joint.

OBJECTIVES: To evaluate the diagnostic efficacy of CBCT-MRI fused images for articular disc calcification of temporomandibular joint (TMJ). MATERIALS AND METHODS: Twenty patients (24 TMJs) whose image examinations showed dense bodies in the TMJ space were included in the study. The locations of dense bodies evaluated by the three experts were used as a reference standard. Three oral and maxillofacial radiology residents evaluated whether the dense bodies were disc calcification or not, with a five-point scale for four sets of images (CBCT alone, MRI alone, both CBCT and MRI observed at a time, and CBCT-MRI fused images) randomly and independently. Each set of images was observed at least 1 week apart. A second evaluation was performed after 4 weeks. Intraclass correlation coefficients were calculated to assess the intra- and inter-observer agreement. The areas under the ROC curves (AUCs) were compared between the four image sets using Z test. RESULTS: Ten cases were determined as articular disc calcifications, and fourteen cases were recognized as loose bodies in the TMJ spaces. The average AUC index for the CBCT-MRI fused images was 0.95 and significantly higher than the other sets (p < 0.01). The intra- and inter-observer agreement in the CBCT-MRI fused images (0.90-0.91, 0.93) was excellent and higher than those in the other images. CONCLUSIONS: CBCT-MRI fused images can significantly improve the observers' reliability and accuracy in determining articular disc calcification of the TMJ. CLINICAL RELEVANCE: The multimodality image fusion is feasible in detecting articular disc calcification of the TMJ which are hard to define by CBCT or MRI alone. It can be utilized especially for inexperienced residents to shorten the learning curve and improve diagnostic accuracy.

Sea cucumber genome provides insights into saponin biosynthesis and aestivation regulation.

Echinoderms exhibit several fascinating evolutionary innovations that are rarely seen in the animal kingdom, but how these animals attained such features is not well understood. Here we report the sequencing and analysis of the genome and extensive transcriptomes of the sea cucumber Apostichopus japonicus, a species from a special echinoderm group with extraordinary potential for saponin synthesis, aestivation and organ regeneration. The sea cucumber does not possess a reorganized Hox cluster as previously assumed for all echinoderms, and the spatial expression of Hox7 and Hox11/13b potentially guides the embryo-to-larva axial transformation. Contrary to the typical production of lanosterol in animal cholesterol synthesis, the oxidosqualene cyclase of sea cucumber produces parkeol for saponin synthesis and has "plant-like" motifs suggestive of convergent evolution. The transcriptional factors Klf2 and Egr1 are identified as key regulators of aestivation, probably exerting their effects through a clock gene-controlled process. Intestinal hypometabolism during aestivation is driven by the DNA hypermethylation of various metabolic gene pathways, whereas the transcriptional network of intestine regeneration involves diverse signaling pathways, including Wnt, Hippo and FGF. Decoding the sea cucumber genome provides a new avenue for an in-depth understanding of the extraordinary features of sea cucumbers and other echinoderms.

Scallop genome reveals molecular adaptations to semi-sessile life and neurotoxins.

Bivalve molluscs are descendants of an early-Cambrian lineage superbly adapted to benthic filter feeding. Adaptations in form and behavior are well recognized, but the underlying molecular mechanisms are largely unknown. Here, we investigate the genome, various transcriptomes, and proteomes of the scallop Chlamys farreri, a semi-sessile bivalve with well-developed adductor muscle, sophisticated eyes, and remarkable neurotoxin resistance. The scallop's large striated muscle is energy-dynamic but not fully differentiated from smooth muscle. Its eyes are supported by highly diverse, intronless opsins expanded by retroposition for broadened spectral sensitivity. Rapid byssal secretion is enabled by a specialized foot and multiple proteins including expanded tyrosinases. The scallop uses hepatopancreas to accumulate neurotoxins and kidney to transform to high-toxicity forms through expanded sulfotransferases, probably as deterrence against predation, while it achieves neurotoxin resistance through point mutations in sodium channels. These findings suggest that expansion and mutation of those genes may have profound effects on scallop's phenotype and adaptation.

Scallop genome provides insights into evolution of bilaterian karyotype and development.

Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.

Whole-Genome Restriction Mapping by "Subhaploid"-Based RAD Sequencing: An Efficient and Flexible Approach for Physical Mapping and Genome Scaffolding.

Assembly of complex genomes using short reads remains a major challenge, which usually yields highly fragmented assemblies. Generation of ultradense linkage maps is promising for anchoring such assemblies, but traditional linkage mapping methods are hindered by the infrequency and unevenness of meiotic recombination that limit attainable map resolution. Here we develop a sequencing-based "in vitro" linkage mapping approach (called RadMap), where chromosome breakage and segregation are realized by generating hundreds of "subhaploid" fosmid/bacterial-artificial-chromosome clone pools, and by restriction site-associated DNA sequencing of these clone pools to produce an ultradense whole-genome restriction map to facilitate genome scaffolding. A bootstrap-based minimum spanning tree algorithm is developed for grouping and ordering of genome-wide markers and is implemented in a user-friendly, integrated software package (AMMO). We perform extensive analyses to validate the power and accuracy of our approach in the model plant Arabidopsis thaliana and human. We also demonstrate the utility of RadMap for enhancing the contiguity of a variety of whole-genome shotgun assemblies generated using either short Illumina reads (300 bp) or long PacBio reads (6-14 kb), with up to 15-fold improvement of N50 (∼816 kb-3.7 Mb) and high scaffolding accuracy (98.1-98.5%). RadMap outperforms BioNano and Hi-C when input assembly is highly fragmented (contig N50 = 54 kb). RadMap can capture wide-range contiguity information and provide an efficient and flexible tool for high-resolution physical mapping and scaffolding of highly fragmented assemblies.

Long Non-Coding RNAs (lncRNAs) of Sea Cucumber: Large-Scale Prediction, Expression Profiling, Non-Coding Network Construction, and lncRNA-microRNA-Gene Interaction Analysis of lncRNAs in Apostichopus japonicus and Holothuria glaberrima During LPS Challenge and Radial Organ Complex Regeneration.

Long non-coding RNA (lncRNA) structurally resembles mRNA but cannot be translated into protein. Although the systematic identification and characterization of lncRNAs have been increasingly reported in model species, information concerning non-model species is still lacking. Here, we report the first systematic identification and characterization of lncRNAs in two sea cucumber species: (1) Apostichopus japonicus during lipopolysaccharide (LPS) challenge and in heathy tissues and (2) Holothuria glaberrima during radial organ complex regeneration, using RNA-seq datasets and bioinformatics analysis. We identified A. japonicus and H. glaberrima lncRNAs that were differentially expressed during LPS challenge and radial organ complex regeneration, respectively. Notably, the predicted lncRNA-microRNA-gene trinities revealed that, in addition to targeting protein-coding transcripts, miRNAs might also target lncRNAs, thereby participating in a potential novel layer of regulatory interactions among non-coding RNA classes in echinoderms. Furthermore, the constructed coding-non-coding network implied the potential involvement of lncRNA-gene interactions during the regulation of several important genes (e.g., Toll-like receptor 1 [TLR1] and transglutaminase-1 [TGM1]) in response to LPS challenge and radial organ complex regeneration in sea cucumbers. Overall, this pioneer systematic identification, annotation, and characterization of lncRNAs in echinoderm pave the way for similar studies and future genetic, genomic, and evolutionary research in non-model species.

Construction of a High-Density Genetic Map and Quantitative Trait Locus Mapping in the Sea Cucumber Apostichopus japonicus.

Genetic linkage maps are critical and indispensable tools in a wide range of genetic and genomic research. With the advancement of genotyping-by-sequencing (GBS) methods, the construction of a high-density and high-resolution linkage maps has become achievable in marine organisms lacking sufficient genomic resources, such as echinoderms. In this study, high-density, high-resolution genetic map was constructed for a sea cucumber species, Apostichopus japonicus, utilizing the 2b-restriction site-associated DNA (2b-RAD) method. A total of 7839 markers were anchored to the linkage map with the map coverage of 99.57%, to our knowledge, this is the highest marker density among echinoderm species. QTL mapping and association analysis consistently captured one growth-related QTL located in a 5 cM region of linkage group (LG) 5. An annotated candidate gene, retinoblastoma-binding protein 5 (RbBP5), which has been reported to be an important regulator of cell proliferation, was recognized in the QTL region. This linkage map represents a powerful tool for research involving both fine-scale QTL mapping and marker assisted selection (MAS), and will facilitate chromosome assignment and improve the whole-genome assembly of sea cucumber in the future.