BFE-Net: bilateral fusion enhanced network for gastrointestinal polyp segmentation.

Accurate segmentation of polyp regions in gastrointestinal endoscopic images is pivotal for diagnosis and treatment. Despite advancements, challenges persist, like accurately segmenting small polyps and maintaining accuracy when polyps resemble surrounding tissues. Recent studies show the effectiveness of the pyramid vision transformer (PVT) in capturing global context, yet it may lack detailed information. Conversely, U-Net excels in semantic extraction. Hence, we propose the bilateral fusion enhanced network (BFE-Net) to address these challenges. Our model integrates U-Net and PVT features via a deep feature enhancement fusion module (FEF) and attention decoder module (AD). Experimental results demonstrate significant improvements, validating our model's effectiveness across various datasets and modalities, promising advancements in gastrointestinal polyp diagnosis and treatment.

Single-Image-Based Deep Learning for Segmentation of Early Esophageal Cancer Lesions.

Accurate segmentation of lesions is crucial for diagnosis and treatment of early esophageal cancer (EEC). However, neither traditional nor deep learning-based methods up to today can meet the clinical requirements, with the mean Dice score - the most important metric in medical image analysis - hardly exceeding 0.75. In this paper, we present a novel deep learning approach for segmenting EEC lesions. Our method stands out for its uniqueness, as it relies solely on a single input image from a patient, forming the so-called "You-Only-Have-One" (YOHO) framework. On one hand, this "one-image-one-network" learning ensures complete patient privacy as it does not use any images from other patients as the training data. On the other hand, it avoids nearly all generalization-related problems since each trained network is applied only to the same input image itself. In particular, we can push the training to "over-fitting" as much as possible to increase the segmentation accuracy. Our technical details include an interaction with clinical doctors to utilize their expertise, a geometry-based data augmentation over a single lesion image to generate the training dataset (the biggest novelty), and an edge-enhanced UNet. We have evaluated YOHO over an EEC dataset collected by ourselves and achieved a mean Dice score of 0.888, which is much higher as compared to the existing deep-learning methods, thus representing a significant advance toward clinical applications. The code and dataset are available at: https://github.com/lhaippp/YOHO.

A systematic review on diagnosis and treatment of gastrointestinal diseases by magnetically controlled capsule endoscopy and artificial intelligence.

Background: Magnetically controlled capsule endoscopy (MCCE) is a non-invasive, painless, comfortable, and safe equipment to diagnose gastrointestinal diseases (GID), partially overcoming the shortcomings of conventional endoscopy and wireless capsule endoscopy (WCE). With advancements in technology, the main technical parameters of MCCE have continuously been improved, and MCCE has become more intelligent. Objectives: The aim of this systematic review was to summarize the research progress of MCCE and artificial intelligence (AI) in the diagnosis and treatment of GID. Data Sources and Methods: We conducted a systematic search of PubMed and EMBASE for published studies on GID detection of MCCE, physical factors related to MCCE imaging quality, the application of AI in aiding MCCE, and its additional functions. We synergistically reviewed the included studies, extracted relevant data, and made comparisons. Results: MCCE was confirmed to have the same performance as conventional gastroscopy and WCE in detecting common GID, while it lacks research in detecting early gastric cancer (EGC). The body position and cleanliness of the gastrointestinal tract are the main factors affecting imaging quality. The applications of AI in screening intestinal diseases have been comprehensive, while in the detection of common gastric diseases such as ulcers, it has been developed. MCCE can perform some additional functions, such as observations of drug behavior in the stomach and drug damage to the gastric mucosa. Furthermore, it can be improved to perform a biopsy. Conclusion: This comprehensive review showed that the MCCE technology has made great progress, but studies on GID detection and treatment by MCCE are in the primary stage. Further studies are required to confirm the performance of MCCE.

Comparison of miRNA transcriptome of exosomes in three categories of somatic cells with derived iPSCs.

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) through epigenetic manipulation. While the essential role of miRNA in reprogramming and maintaining pluripotency is well studied, little is known about the functions of miRNA from exosomes in this context. To fill this research gap,we comprehensively obtained the 17 sets of cellular mRNA transcriptomic data with 3.93 × 1010 bp raw reads and 18 sets of exosomal miRNA transcriptomic data with 2.83 × 107 bp raw reads from three categories of human somatic cells: peripheral blood mononuclear cells (PBMCs), skin fibroblasts(SFs) and urine cells (UCs), along with their derived iPSCs. Additionally, differentially expressed molecules of each category were identified and used to perform gene set enrichment analysis. Our study provides sets of comparative transcriptomic data of cellular mRNA and exosomal miRNA from three categories of human tissue with three individual biological controls in studies of iPSCs generation, which will contribute to a better understanding of donor cell variation in functional epigenetic regulation and differentiation bias in iPSCs.

Quantitative Analysis on Molecular Characteristics Evolution of Gastric Cancer Progression and Prognosis.

The dynamic changes of key biological characteristics from gastric low-grade intraepithelial neoplasia (LGIN) to high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC) are still unclear, which greatly affect the accurate diagnosis and treatment of EGC and prognosis evaluation of gastric cancer (GC). In this study, bioinformatics methods/tools are applied to quantitatively analyze molecular characteristics evolution of GC progression, and a prognosis model is constructed. This study finds that some dysregulated differentially expressed mRNAs (DEmRNAs) in the LGIN stage may continue to promote the occurrence and development of EGC. Among the LGIN, HGIN, and EGC stages, there are differences and relevance in the transcription expression patterns of DEmRNAs, and the activation related to immune cells is very different. The biological functions continuously changed during the progression from LGIN to HGIN to EGC. The COX model constructed based on the three EGC-related DEmRNAs has GC prognostic risk prediction ability. The evolution of biological characteristics during the development of EGC mined by the authors provides new insight into understanding the molecular mechanism of EGC occurrence and development. The three-gene prognostic risk model provides a new method for assisting GC clinical treatment decisions.

Early gastric cancer segmentation in gastroscopic images using a co-spatial attention and channel attention based triple-branch ResUnet.

BACKGROUND AND OBJECTIVE: The artificial segmentation of early gastric cancer (EGC) lesions in gastroscopic images remains a challenging task due to reasons including the diversity of mucosal features, irregular edges of EGC lesions and nuances between EGC lesions and healthy background mucosa. Hence, this study proposed an automatic segmentation framework: co-spatial attention and channel attention based triple-branch ResUnet (CSA-CA-TB-ResUnet) to achieve accurate segmentation of EGC lesions for aiding clinical diagnosis and treatment. METHODS: The input gastroscopic image sequences of the triple-branch segmentation network CSA-CA-TB-ResUnet is firstly generated by the designed multi-branch input preprocessing (MBIP) module in order to fully utilize massive correlation information among multiple gastroscopic images of the same a lesion. Then, the proposed CSA-CA-TB-ResUnet performs the segmentation of EGC lesion, in which the co-spatial attention (CSA) mechanism is designed to activate the spatial location of EGC lesions by leveraging on the correlations among multiple gastroscopic images of the same EGC lesion, and the channel attention (CA) mechanism is introduced to extract subtle discriminative features of EGC lesions by capturing the interdependencies between channel features. Finally, two gastroscopic images datasets from different digestive endoscopic centers in the southwest and northeast regions of China respectively were collected to validate the performances of proposed segmentation method. RESULTS: The correlation information among gastroscopic images was confirmed to be able to improve the accuracy of EGC segmentation. On another unseen dataset, our EGC segmentation method achieves Jaccard similarity index (JSI) of 84.54% (95% confidence interval (CI), 83.49%-85.56%), threshold Jaccard index (TJI) of 81.73% (95% CI, 79.70%-83.61%), Dice similarity coefficient (DSC) of 91.08% (95% CI, 90.40%-91.76%) and pixel-wise accuracy (PA) of 91.18% (95% CI, 90.43%-91.87%), which is superior to other state-of-the-art methods. Even on the challenging small lesions, the segmentation results of our CSA-CA-TB-ResUnet-based method are consistently and significantly better than other state-of-the-art methods. We also compared the segmentation result of our model with the diagnostic accuracy with junior/senior expert. The comparison results indicated that our model performed better than the junior expert. CONCLUSIONS: This study proposed a novel CSA-CA-TB-ResUnet-based EGC segmentation method and it has a potential for real-time application in improving EGC clinical diagnosis and minimally invasive surgery.

Semi-Supervised Segmentation Framework for Gastrointestinal Lesion Diagnosis in Endoscopic Images.

BACKGROUND: Accurate gastrointestinal (GI) lesion segmentation is crucial in diagnosing digestive tract diseases. An automatic lesion segmentation in endoscopic images is vital to relieving physicians' burden and improving the survival rate of patients. However, pixel-wise annotations are highly intensive, especially in clinical settings, while numerous unlabeled image datasets could be available, although the significant results of deep learning approaches in several tasks heavily depend on large labeled datasets. Limited labeled data also hinder trained models' generalizability under fully supervised learning for computer-aided diagnosis (CAD) systems. METHODS: This work proposes a generative adversarial learning-based semi-supervised segmentation framework for GI lesion diagnosis in endoscopic images to tackle the challenge of limited annotations. The proposed approach leverages limited annotated and large unlabeled datasets in the training networks. We extensively tested the proposed method on 4880 endoscopic images. RESULTS: Compared with current related works, the proposed method validates better results (Dice similarity coefficient = 89.42 ± 3.92, Intersection over union = 80.04 ± 5.75, Precision = 91.72 ± 4.05, Recall = 90.11 ± 5.64, and Hausdorff distance = 23.28 ± 14.36) on the challenging multi-sited datasets, confirming the effectiveness of the proposed framework. CONCLUSION: We explore a semi-supervised lesion segmentation method to employ the full use of multiple unlabeled endoscopic images to improve lesion segmentation accuracy. Experimental results confirmed the potential of our method and outperformed promising results compared with the current related works. The proposed CAD system can minimize diagnostic errors.

Risk factors and a predictive nomogram for lymph node metastasis in superficial esophageal squamous cell carcinoma.

BACKGROUND: Superficial esophageal squamous cell carcinoma (ESCC) is defined as cancer infiltrating the mucosa and submucosa, regardless of regional lymph node metastasis (LNM). Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM. Patients with a high risk of LNM always need further treatment after endoscopic resection. Therefore, accurately assessing the risk of LNM is critical for additional treatment options. AIM: To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients. METHODS: Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1, 2009 to January 31, 2016 were collected. Logistic regression analysis was used to predict LNM risk factors, and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to obtain the accuracy of the nomogram model. RESULTS: A total of 4660 patients with esophageal cancer underwent esophagectomy. Of these, 474 superficial ESCC patients were enrolled in the final analysis, with 322 patients in the training set and 142 patients in the validation set. The prevalence of LNM was 3.29% (5/152) for intramucosal cancer and increased to 26.40% (85/322) for submucosal cancer. Multivariate logistic analysis showed that tumor size, invasive depth, tumor differentiation, infiltrative growth pattern, tumor budding, and lymphovascular invasion were significantly correlated with LNM. A nomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789 (95%CI: 0.737-0.841) in the training set and 0.827 (95%CI: 0.755-0.899) in the validation set. CONCLUSION: We developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitate additional decision-making in treating patients who undergo endoscopic resection.

Examining the effect of synthetic data augmentation in polyp detection and segmentation.

PURPOSE: As with several medical image analysis tasks based on deep learning, gastrointestinal image analysis is plagued with data scarcity, privacy concerns and an insufficient number of pathology samples. This study examines the generation and utility of synthetic samples of colonoscopy images with polyps for data augmentation. METHODS: We modify and train a pix2pix model to generate synthetic colonoscopy samples with polyps to augment the original dataset. Subsequently, we create a variety of datasets by varying the quantity of synthetic samples and traditional augmentation samples, to train a U-Net network and Faster R-CNN model for segmentation and detection of polyps, respectively. We compare the performance of the models when trained with the resulting datasets in terms of F1 score, intersection over union, precision and recall. Further, we compare the performances of the models with unseen polyp datasets to assess their generalization ability. RESULTS: The average F1 coefficient and intersection over union are improved with increasing number of synthetic samples in U-Net over all test datasets. The performance of the Faster R-CNN model is also improved in terms of polyp detection, while decreasing the false-negative rate. Further, the experimental results for polyp detection outperform similar studies in the literature on the ETIS-PolypLaribDB dataset. CONCLUSION: By varying the quantity of synthetic and traditional augmentation, there is the potential to control the sensitivity of deep learning models in polyp segmentation and detection. Further, GAN-based augmentation is a viable option for improving the performance of models for polyp segmentation and detection.

Time to infer miRNA sponge modules.

Inferring competing endogenous RNA (ceRNA) or microRNA (miRNA) sponge modules is a challenging and meaningful task for revealing ceRNA regulation mechanism at the module level. Modules in this context refer to groups of miRNA sponges which have mutual competitions and act as functional units for achieving biological processes. The recent development of computational methods based on heterogeneous data provides a novel way to discern the competitive effects of miRNA sponges on human complex diseases. This article aims to provide a comprehensive perspective of miRNA sponge module discovery methods. We first review the publicly available databases of cancer-related miRNA sponges, as the miRNA sponges involved in human cancers contribute to the discovery of cancer-associated modules. Then we review the existing computational methods for inferring miRNA sponge modules. Furthermore, we conduct an assessment on the performance of the module discovery methods with the pan-cancer dataset, and the comparison study indicates that it is useful to infer biologically meaningful miRNA sponge modules by directly mapping heterogeneous data to the competitive modules. Finally, we discuss the future directions and associated challenges in developing in silico methods to infer miRNA sponge modules. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

Brain Fingerprinting and Lie Detection: A Study of Dynamic Functional Connectivity Patterns of Deception Using EEG Phase Synchrony Analysis.

This study investigated the brain functional connectivity (FC) patterns related to lie detection (LD) tasks with the purpose of analyzing the underlying cognitive processes and mechanisms in deception. Using the guilty knowledge test protocol, 30 subjects were divided randomly into guilty and innocent groups, and their electroencephalogram (EEG) signals were recorded on 32 electrodes. Phase synchrony of EEG was analyzed between different brain regions. A few-trials-based relative phase synchrony (FTRPS) measure was proposed to avoid the false synchronization that occurs due to volume conduction. FTRPS values with a significantly statistical difference between two groups were employed to construct FC patterns of deception, and the FTRPS values from the FC networks were extracted as the features for the training and testing of the support vector machine. Finally, four more intuitive brain fingerprinting graphs (BFG) on delta, theta, alpha and beta bands were respectively proposed. The experimental results reveal that deceptive responses elicited greater oscillatory synchronization than truthful responses between different brain regions, which plays an important role in executing lying tasks. The functional connectivity in the BFG is mainly implicated in the visuo-spatial imagery, bottom-top attention and memory systems, work memory and episodic encoding, and top-down attention and inhibition processing. These may, in part, underlie the mechanism of communication between different brain cortices during lying. High classification accuracy demonstrates the validation of BFG to identify deception behavior, and suggests that the proposed FTRPS could be a sensitive measure for LD in the real application.

Analysis of ECG Signals by Dynamic Mode Decomposition.

OBJECTIVE: Based on cybernetics, a large system can be divided into subsystems, and the stability of each can determine the overall properties of the system. However, this stability analysis perspective has not yet been employed in electrocardiogram (ECG) signals. This is the first study to attempt to evaluate whether the stability of decomposed ECG subsystems can be analyzed in order to effectively investigate the overall performance of ECG signals, and aid in disease diagnosis. METHODS: We used seven different cardiac pathologies (myocardial infarction, cardiomyopathy, bundle branch block, dysrhythmia, hypertrophy, myocarditis, and valvular heart disease) to illustrate our method. Dynamic mode decomposition (DMD) was first used to decompose ECG signals into dynamic modes (DMs) which can be regarded as ECG subsystems. Then, the features related to the DMs stabilities were extracted, and nine common classifiers were implemented for classification of these pathologies. RESULTS: Most features were significant for differentiating the above-mentioned groups (p value<0.05 after Bonferroni correction). In addition, our method outperformed all existing methods for cardiac pathology classification. CONCLUSION: We have provided a new spatial and temporal decomposition method, namely DMD, to study ECG signals. SIGNIFICANCE: Our method can reveal new cardiac mechanisms, which can contribute to the comprehensive understanding of its underlying mechanisms and disease diagnosis, and thus, can be widely used for ECG signal analysis in the future.

Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data.

BACKGROUND: Existing computational methods for studying miRNA regulation are mostly based on bulk miRNA and mRNA expression data. However, bulk data only allows the analysis of miRNA regulation regarding a group of cells, rather than the miRNA regulation unique to individual cells. Recent advance in single-cell miRNA-mRNA co-sequencing technology has opened a way for investigating miRNA regulation at single-cell level. However, as currently single-cell miRNA-mRNA co-sequencing data is just emerging and only available at small-scale, there is a strong need of novel methods to exploit existing single-cell data for the study of cell-specific miRNA regulation. RESULTS: In this work, we propose a new method, CSmiR (Cell-Specific miRNA regulation) to combine single-cell miRNA-mRNA co-sequencing data and putative miRNA-mRNA binding information to identify miRNA regulatory networks at the resolution of individual cells. We apply CSmiR to the miRNA-mRNA co-sequencing data in 19 K562 single-cells to identify cell-specific miRNA-mRNA regulatory networks for understanding miRNA regulation in each K562 single-cell. By analyzing the obtained cell-specific miRNA-mRNA regulatory networks, we observe that the miRNA regulation in each K562 single-cell is unique. Moreover, we conduct detailed analysis on the cell-specific miRNA regulation associated with the miR-17/92 family as a case study. The comparison results indicate that CSmiR is effective in predicting cell-specific miRNA targets. Finally, through exploring cell-cell similarity matrix characterized by cell-specific miRNA regulation, CSmiR provides a novel strategy for clustering single-cells and helps to understand cell-cell crosstalk. CONCLUSIONS: To the best of our knowledge, CSmiR is the first method to explore miRNA regulation at a single-cell resolution level, and we believe that it can be a useful method to enhance the understanding of cell-specific miRNA regulation.

Improving the Classification Performance of Esophageal Disease on Small Dataset by Semi-supervised Efficient Contrastive Learning.

The classification of esophageal disease based on gastroscopic images is important in the clinical treatment, and is also helpful in providing patients with follow-up treatment plans and preventing lesion deterioration. In recent years, deep learning has achieved many satisfactory results in gastroscopic image classification tasks. However, most of them need a training set that consists of large numbers of images labeled by experienced experts. To reduce the image annotation burdens and improve the classification ability on small labeled gastroscopic image datasets, this study proposed a novel semi-supervised efficient contrastive learning (SSECL) classification method for esophageal disease. First, an efficient contrastive pair generation (ECPG) module was proposed to generate efficient contrastive pairs (ECPs), which took advantage of the high similarity features of images from the same lesion. Then, an unsupervised visual feature representation containing the general feature of esophageal gastroscopic images is learned by unsupervised efficient contrastive learning (UECL). At last, the feature representation will be transferred to the down-stream esophageal disease classification task. The experimental results have demonstrated that the classification accuracy of SSECL is 92.57%, which is better than that of the other state-of-the-art semi-supervised methods and is also higher than the classification method based on transfer learning (TL) by 2.28%. Thus, SSECL has solved the challenging problem of improving the classification result on small gastroscopic image dataset by fully utilizing the unlabeled gastroscopic images and the high similarity information among images from the same lesion. It also brings new insights into medical image classification tasks.

mRBioM: An Algorithm for the Identification of Potential mRNA Biomarkers From Complete Transcriptomic Profiles of Gastric Adenocarcinoma.

PURPOSE: In this work, an algorithm named mRBioM was developed for the identification of potential mRNA biomarkers (PmBs) from complete transcriptomic RNA profiles of gastric adenocarcinoma (GA). METHODS: mRBioM initially extracts differentially expressed (DE) RNAs (mRNAs, miRNAs, and lncRNAs). Next, mRBioM calculates the total information amount of each DE mRNA based on the coexpression network, including three types of RNAs and the protein-protein interaction network encoded by DE mRNAs. Finally, PmBs were identified according to the variation trend of total information amount of all DE mRNAs. Four PmB-based classifiers without learning and with learning were designed to discriminate the sample types to confirm the reliability of PmBs identified by mRBioM. PmB-based survival analysis was performed. Finally, three other cancer datasets were used to confirm the generalization ability of mRBioM. RESULTS: mRBioM identified 55 PmBs (41 upregulated and 14 downregulated) related to GA. The list included thirteen PmBs that have been verified as biomarkers or potential therapeutic targets of gastric cancer, and some PmBs were newly identified. Most PmBs were primarily enriched in the pathways closely related to the occurrence and development of gastric cancer. Cancer-related factors without learning achieved sensitivity, specificity, and accuracy of 0.90, 1, and 0.90, respectively, in the classification of the GA and control samples. Average accuracy, sensitivity, and specificity of the three classifiers with machine learning ranged within 0.94-0.98, 0.94-0.97, and 0.97-1, respectively. The prognostic risk score model constructed by 4 PmBs was able to correctly and significantly (∗∗∗ p < 0.001) classify 269 GA patients into the high-risk (n = 134) and low-risk (n = 135) groups. GA equivalent classification performance was achieved using the complete transcriptomic RNA profiles of colon adenocarcinoma, lung adenocarcinoma, and hepatocellular carcinoma using PmBs identified by mRBioM. CONCLUSIONS: GA-related PmBs have high specificity and sensitivity and strong prognostic risk prediction. MRBioM has also good generalization. These PmBs may have good application prospects for early diagnosis of GA and may help to elucidate the mechanism governing the occurrence and development of GA. Additionally, mRBioM is expected to be applied for the identification of other cancer-related biomarkers.

Automatic classification of esophageal disease in gastroscopic images using an efficient channel attention deep dense convolutional neural network.

The accurate diagnosis of various esophageal diseases at different stages is crucial for providing precision therapy planning and improving 5-year survival rate of esophageal cancer patients. Automatic classification of various esophageal diseases in gastroscopic images can assist doctors to improve the diagnosis efficiency and accuracy. The existing deep learning-based classification method can only classify very few categories of esophageal diseases at the same time. Hence, we proposed a novel efficient channel attention deep dense convolutional neural network (ECA-DDCNN), which can classify the esophageal gastroscopic images into four main categories including normal esophagus (NE), precancerous esophageal diseases (PEDs), early esophageal cancer (EEC) and advanced esophageal cancer (AEC), covering six common sub-categories of esophageal diseases and one normal esophagus (seven sub-categories). In total, 20,965 gastroscopic images were collected from 4,077 patients and used to train and test our proposed method. Extensive experiments results have demonstrated convincingly that our proposed ECA-DDCNN outperforms the other state-of-art methods. The classification accuracy (Acc) of our method is 90.63% and the averaged area under curve (AUC) is 0.9877. Compared with other state-of-art methods, our method shows better performance in the classification of various esophageal disease. Particularly for these esophageal diseases with similar mucosal features, our method also achieves higher true positive (TP) rates. In conclusion, our proposed classification method has confirmed its potential ability in a wide variety of esophageal disease diagnosis.

miRSM: an R package to infer and analyse miRNA sponge modules in heterogeneous data.

In molecular biology, microRNA (miRNA) sponges are RNA transcripts which compete with other RNA transcripts for binding with miRNAs. Research has shown that miRNA sponges have a fundamental impact on tissue development and disease progression. Generally, to achieve a specific biological function, miRNA sponges tend to form modules or communities in a biological system. Until now, however, there is still a lack of tools to aid researchers to infer and analyse miRNA sponge modules from heterogeneous data. To fill this gap, we develop an R/Bioconductor package, miRSM, for facilitating the procedure of inferring and analysing miRNA sponge modules. miRSM provides a collection of 50 co-expression analysis methods to identify gene co-expression modules (which are candidate miRNA sponge modules), four module discovery methods to infer miRNA sponge modules and seven modular analysis methods for investigating miRNA sponge modules. miRSM will enable researchers to quickly apply new datasets to infer and analyse miRNA sponge modules, and will consequently accelerate the research on miRNA sponges.

CEG 2.0: an updated database of clusters of essential genes including eukaryotic organisms.

Essential genes are key elements for organisms to maintain their living. Building databases that store essential genes in the form of homologous clusters, rather than storing them as a singleton, can provide more enlightening information such as the general essentiality of homologous genes in multiple organisms. In 2013, the first database to store prokaryotic essential genes in clusters, CEG (Clusters of Essential Genes), was constructed. Afterward, the amount of available data for essential genes increased by a factor >3 since the last revision. Herein, we updated CEG to version 2, including more prokaryotic essential genes (from 16 gene datasets to 29 gene datasets) and newly added eukaryotic essential genes (nine species), specifically the human essential genes of 12 cancer cell lines. For prokaryotes, information associated with drug targets, such as protein structure, ligand-protein interaction, virulence factor and matched drugs, is also provided. Finally, we provided the service of essential gene prediction for both prokaryotes and eukaryotes. We hope our updated database will benefit more researchers in drug targets and evolutionary genomics. Database URL: http://cefg.uestc.cn/ceg.

LMSM: A modular approach for identifying lncRNA related miRNA sponge modules in breast cancer.

Until now, existing methods for identifying lncRNA related miRNA sponge modules mainly rely on lncRNA related miRNA sponge interaction networks, which may not provide a full picture of miRNA sponging activities in biological conditions. Hence there is a strong need of new computational methods to identify lncRNA related miRNA sponge modules. In this work, we propose a framework, LMSM, to identify LncRNA related MiRNA Sponge Modules from heterogeneous data. To understand the miRNA sponging activities in biological conditions, LMSM uses gene expression data to evaluate the influence of the shared miRNAs on the clustered sponge lncRNAs and mRNAs. We have applied LMSM to the human breast cancer (BRCA) dataset from The Cancer Genome Atlas (TCGA). As a result, we have found that the majority of LMSM modules are significantly implicated in BRCA and most of them are BRCA subtype-specific. Most of the mediating miRNAs act as crosslinks across different LMSM modules, and all of LMSM modules are statistically significant. Multi-label classification analysis shows that the performance of LMSM modules is significantly higher than baseline's performance, indicating the biological meanings of LMSM modules in classifying BRCA subtypes. The consistent results suggest that LMSM is robust in identifying lncRNA related miRNA sponge modules. Moreover, LMSM can be used to predict miRNA targets. Finally, LMSM outperforms a graph clustering-based strategy in identifying BRCA-related modules. Altogether, our study shows that LMSM is a promising method to investigate modular regulatory mechanism of sponge lncRNAs from heterogeneous data.

Correction to: Identifying miRNA synergism using multiple-intervention causal inference.

After publication of this supplement article [1], it was brought to our attention that the Fig. 3 was incorrect. The correct Fig. 3 is as below.