Glycocylation represents the most complex and widespread post-translational modifications in human proteins. The variation of glycosylation is closely related to oncogenic transformation. Therefore, profiling of glycans detached from proteins is a promising strategy to identify biomarkers for cancer detection. This study identified candidate glycan biomarkers associated with hepatocellular carcinoma by mass spectrometry. Specifically, mass spectrometry data were analyzed with a peak selection procedure which incorporates multiple random sampling strategies with recursive feature selection based on support vector machines. Ten peak sets were obtained from different combinations of samples. Seven peaks were shared by each of the 10 peaksets, in which 7-12 peaks were selected, indicating 58-100% of peaks were shared by the 10 peaksets. Support vector machines and hierarchical clustering method were used to evaluate the performance of the peaksets. The predictive performance of the seven peaks was further evaluated by using 19 newly generated MALDI-TOF spectra. Glycan structures for four glycans of the seven peaks were determined. Literature search indicated that the structures of the four glycans could be found in some cancerrelated glycoproteins. The method of this study is significant in deriving consistent, accurate, and biological significant glycan marker candidates for hepatocellular carcinoma diagnosis.

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Objective:To evaluate the performance of a deep learning system (DLS) in classifying the severity of papilledema associated with increased intracranial pressure, on standard retinal fundus photographs.Methods:A DLS was trained to automatically classify papilledema severity in 965 patients (2103 mydriatic fundus photographs), representing a multiethnic cohort of patients with confirmed elevated intracranial pressure. Training was performed on 1052 photographs with mild/moderate papilledema (MP) and 1051 photographs with severe papilledema (SP) classified by a panel of experts. The performance of the DLS and that of three independent neuro-ophthalmologists were tested in 111 patients (214 photographs, 92 with MP and 122 with SP), by calculating the area under the receiver operating characteristics curve (AUC), accuracy, sensitivity and specificity. Kappa agreement scores between the DLS and each of the three graders and among the three graders were calculated.Results:The DLS successfully discriminated between photographs of MP and SP, with an AUC of 0.93 (95%CI: 0.89-0.96) and an accuracy, sensitivity and specificity of 87.9%, 91.8% and 86.2%, respectively. This performance was comparable with that of the three neuro-ophthalmologists (84.1%, 91.8% and 73.9%, P=0.19, P=1, P=0.09, respectively). Misclassification by the DLS was mainly observed for moderate papilledema (Frisén grade 3). Agreement scores between the DLS and the neuro-ophthalmologists’ evaluation was 0.62 (CI 95% 0.57-0.68), whereas the inter-grader agreement among the three neuro-ophthalmologists was 0.54 (CI 95% 0.47-0.62).Conclusions:Our DLS accurately classified the severity of papilledema on an independent set of mydriatic fundus photographs, achieving a comparable performance with that of independent neuro-ophthalmologists.Classification of Evidence:This study provides Class II evidence that a deep learning system using mydriatic retinal fundus photographs accurately classified the severity of papilledema associated in patients with a diagnosis of increased intracranial pressure.

Major histocompatibility complex (MHC)-binding peptides are essential for antigen recognition by T-cell receptors and are being explored for vaccine design. Computational methods have been developed for predicting MHC-binding peptides of fixed lengths, based on the training of relatively few non-binders. It is desirable to introduce methods applicable for peptides of flexible lengths and trained by using more diverse sets of non-binders. MHC-BPS is a web-based MHC-binder prediction server that uses support vector machines for predicting peptide binders of flexible lengths for 18 MHC class I and 12 class II alleles from sequence-derived physicochemical properties, which were trained by using 4,208 approximately 3,252 binders and 234,333 approximately 168,793 non-binders, and evaluated by an independent set of 545 approximately 476 binders and 110,564 approximately 84,430 non-binders. The binder prediction accuracies are 86 approximately 99% for 25 and 70 approximately 80% for five alleles, and the non-binder accuracies are 96 approximately 99% for 30 alleles. A screening of HIV-1 genome identifies 0.01 approximately 5% and 5 approximately 8% of the constituent peptides as binders for 24 and 6 alleles, respectively, including 75 approximately 100% of the known epitopes. This method correctly predicts 73.3% of the 15 newly published epitopes in the last 4 months of 2005. MHC-BPS is available at http://bidd.cz3.nus.edu.sg/mhc/ .