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General General

Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning.

In Scientific reports ; h5-index 158.0

The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.

Manjang Kalifa, Tripathi Shailesh, Yli-Harja Olli, Dehmer Matthias, Glazko Galina, Emmert-Streib Frank


oncology Oncology

Application of artificial intelligence in chronic liver diseases: a systematic review and meta-analysis.

In BMC gastroenterology

BACKGROUND : The gold standard for the diagnosis of liver fibrosis and nonalcoholic fatty liver disease (NAFLD) is liver biopsy. Various noninvasive modalities, e.g., ultrasonography, elastography and clinical predictive scores, have been used as alternatives to liver biopsy, with limited performance. Recently, artificial intelligence (AI) models have been developed and integrated into noninvasive diagnostic tools to improve their performance.

METHODS : We systematically searched for studies on AI-assisted diagnosis of liver fibrosis and NAFLD on MEDLINE, Scopus, Web of Science and Google Scholar. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic odds ratio (DOR) with their 95% confidence intervals (95% CIs) were calculated using a random effects model. A summary receiver operating characteristic curve and the area under the curve was generated to determine the diagnostic accuracy of the AI-assisted system. Subgroup analyses by diagnostic modalities, population and AI classifiers were performed.

RESULTS : We included 19 studies reporting the performances of AI-assisted ultrasonography, elastrography, computed tomography, magnetic resonance imaging and clinical parameters for the diagnosis of liver fibrosis and steatosis. For the diagnosis of liver fibrosis, the pooled sensitivity, specificity, PPV, NPV and DOR were 0.78 (0.71-0.85), 0.89 (0.81-0.94), 0.72 (0.58-0.83), 0.92 (0.88-0.94) and 31.58 (11.84-84.25), respectively, for cirrhosis; 0.86 (0.80-0.90), 0.87 (0.80-0.92), 0.85 (0.75-0.91), 0.88 (0.82-0.92) and 37.79 (16.01-89.19), respectively; for advanced fibrosis; and 0.86 (0.78-0.92), 0.81 (0.77-0.84), 0.88 (0.80-0.93), 0.77 (0.58-0.89) and 26.79 (14.47-49.62), respectively, for significant fibrosis. Subgroup analyses showed significant differences in performance for the diagnosis of fibrosis among different modalities. The pooled sensitivity, specificity, PPV, NPV and DOR were 0.97 (0.76-1.00), 0.91 (0.78-0.97), 0.95 (0.87-0.98), 0.93 (0.80-0.98) and 191.52 (38.82-944.81), respectively, for the diagnosis of liver steatosis.

CONCLUSIONS : AI-assisted systems have promising potential for the diagnosis of liver fibrosis and NAFLD. Validations of their performances are warranted before implementing these AI-assisted systems in clinical practice.

TRIAL REGISTRATION : The protocol was registered with PROSPERO (CRD42020183295).

Decharatanachart Pakanat, Chaiteerakij Roongruedee, Tiyarattanachai Thodsawit, Treeprasertsuk Sombat


Artificial intelligence, Cirrhosis, Computer-assisted, Deep learning, Fatty liver, Liver fibrosis, Liver steatosis, Machine learning, NAFLD, Non-invasive diagnostic tests

General General

A review of deep learning applications for genomic selection.

In BMC genomics ; h5-index 78.0

BACKGROUND : Several conventional genomic Bayesian (or no Bayesian) prediction methods have been proposed including the standard additive genetic effect model for which the variance components are estimated with mixed model equations. In recent years, deep learning (DL) methods have been considered in the context of genomic prediction. The DL methods are nonparametric models providing flexibility to adapt to complicated associations between data and output with the ability to adapt to very complex patterns.

MAIN BODY : We review the applications of deep learning (DL) methods in genomic selection (GS) to obtain a meta-picture of GS performance and highlight how these tools can help solve challenging plant breeding problems. We also provide general guidance for the effective use of DL methods including the fundamentals of DL and the requirements for its appropriate use. We discuss the pros and cons of this technique compared to traditional genomic prediction approaches as well as the current trends in DL applications.

CONCLUSIONS : The main requirement for using DL is the quality and sufficiently large training data. Although, based on current literature GS in plant and animal breeding we did not find clear superiority of DL in terms of prediction power compared to conventional genome based prediction models. Nevertheless, there are clear evidences that DL algorithms capture nonlinear patterns more efficiently than conventional genome based. Deep learning algorithms are able to integrate data from different sources as is usually needed in GS assisted breeding and it shows the ability for improving prediction accuracy for large plant breeding data. It is important to apply DL to large training-testing data sets.

Montesinos-López Osval Antonio, Montesinos-López Abelardo, Pérez-Rodríguez Paulino, Barrón-López José Alberto, Martini Johannes W R, Fajardo-Flores Silvia Berenice, Gaytan-Lugo Laura S, Santana-Mancilla Pedro C, Crossa José


Deep learning, Genomic selection, Genomic trends, Plant breeding

General General

Drug-induced cell viability prediction from LINCS-L1000 through WRFEN-XGBoost algorithm.

In BMC bioinformatics

BACKGROUND : Predicting the drug response of the cancer diseases through the cellular perturbation signatures under the action of specific compounds is very important in personalized medicine. In the process of testing drug responses to the cancer, traditional experimental methods have been greatly hampered by the cost and sample size. At present, the public availability of large amounts of gene expression data makes it a challenging task to use machine learning methods to predict the drug sensitivity.

RESULTS : In this study, we introduced the WRFEN-XGBoost cell viability prediction algorithm based on LINCS-L1000 cell signatures. We integrated the LINCS-L1000, CTRP and Achilles datasets and adopted a weighted fusion algorithm based on random forest and elastic net for key gene selection. Then the FEBPSO algorithm was introduced into XGBoost learning algorithm to predict the cell viability induced by the drugs. The proposed method was compared with some new methods, and it was found that our model achieved good results with 0.83 Pearson correlation. At the same time, we completed the drug sensitivity validation on the NCI60 and CCLE datasets, which further demonstrated the effectiveness of our method.

CONCLUSIONS : The results showed that our method was conducive to the elucidation of disease mechanisms and the exploration of new therapies, which greatly promoted the progress of clinical medicine.

Lu Jiaxing, Chen Ming, Qin Yufang


Cell viability, Drug sensitivity, Perturbation signatures, WRFEN-XGBoost algorithm

Radiology Radiology

GroupRegNet: a groupwise one-shot deep learning-based 4D image registration method.

In Physics in medicine and biology

Accurate deformable 4-dimensional (4D) (3-dimensional in space and time) medical images registration is essential in a variety of medical applications. Deep learning-based methods have recently gained popularity in this area for the significantly lower inference time. However, they suffer from drawbacks of non-optimal accuracy and the requirement of a large amount of training data. A new method named GroupRegNet is proposed to address both limitations. The deformation fields to warp all images in the group into a common template is obtained through one-shot learning. The use of the implicit template reduces bias and accumulated error associated with the specified reference image. The one-shot learning strategy is similar to the conventional iterative optimization method but the motion model and parameters are replaced with a convolutional neural network (CNN) and the weights of the network. GroupRegNet also features a simpler network design and a more straightforward registration process, which eliminates the need to break up the input image into patches. The proposed method was quantitatively evaluated on two public respiratory-binned 4D-CT datasets. The results suggest that GroupRegNet outperforms the latest published deep learning-based methods and is comparable to the top conventional method pTVreg. To facilitate future research, the source code is available at

Zhang Yunlu, Wu Xue, Gach H Michael, Li H Harold, Yang Deshan


4D-CT, Deep learning, deformable image registration

Radiology Radiology

Head-and-neck organs-at-risk auto-delineation using dual pyramid networks for CBCT-guided adaptive radiotherapy.

In Physics in medicine and biology

Organ-at-risk (OAR) delineation is a key step for cone-beam CT (CBCT) based adaptive radiotherapy planning that can be a time-consuming, labor-intensive, and subject-to-variability process. We aim to develop a fully automated approach aided by synthetic MRI for rapid and accurate CBCT multi-organ contouring in head-and-neck (HN) cancer patients. MRI has superb soft-tissue contrasts, while CBCT offers bony-structure contrasts. Using the complementary information provided by MRI and CBCT is expected to enable accurate multi-organ segmentation in HN cancer patients. In our proposed method, MR images are firstly synthesized using a pre-trained cycle-consistent generative adversarial network given CBCT. The features of CBCT and synthetic MRI are then extracted using dual pyramid networks for final delineation of organs. CBCT images and their corresponding manual contours were used as pairs to train and test the proposed model. Quantitative metrics including Dice similarity coefficient (DSC), Hausdorff distance 95% (HD95), mean surface distance (MSD), and residual mean square distance (RMS) were used to evaluate the proposed method. The proposed method was evaluated on a cohort of 65 HN cancer patients. CBCT images were collected from those patients who received proton therapy. Overall, DSC values of 0.87±0.03, 0.79±0.10/0.79±0.11, 0.89±0.08/0.89±0.07, 0.90±0.08, 0.75±0.06/0.77±0.06, 0.86±0.13, 0.66±0.14, 0.78±0.05/0.77±0.04, 0.96±0.04, 0.89±0.04/0.89±0.04, 0.83±0.02, and 0.84±0.07 for commonly used OARs for treatment planning including brain stem, left/right cochlea, left/right eye, larynx, left/right lens, mandible, optic chiasm, left/right optic nerve, oral cavity, left/right parotid, pharynx, and spinal cord, respectively, were achieved. In this study, we developed a synthetic MRI-aided HN CBCT auto-segmentation method based on deep learning. It provides a rapid and accurate OAR auto-delineation approach, which can be used for adaptive radiation therapy.

Dai Xianjin, Lei Yang, Wang Tonghe, Dhabaan Anees, McDonald Mark, Beitler Jonathan J, Curran Walter J, Zhou Jun, Liu Tian, Yang Xiaofeng


CBCT, Deep Learning, Head and Neck, Organ Segmentation