CrepHAN: cross-species prediction of enhancers by using hierarchical attention networks.

MOTIVATION: Enhancers are important functional elements in genome sequences. The identification of enhancers is a very challenging task due to the great diversity of enhancer sequences and the flexible localization on genomes. Till now, the interactions between enhancers and genes have not been fully understood yet. To speed up the studies of the regulatory roles of enhancers, computational tools for the prediction of enhancers have emerged in recent years. Especially, thanks to the ENCODE project and the advances of high-throughput experimental techniques, a large amount of experimentally verified enhancers have been annotated on the human genome, which allows large-scale predictions of unknown enhancers using data-driven methods. However, except for human and some model organisms, the validated enhancer annotations are scarce for most species, leading to more difficulties in the computational identification of enhancers for their genomes. RESULTS: In this study, we propose a deep learning-based predictor for enhancers, named CrepHAN, which is featured by a hierarchical attention neural network and word embedding-based representations for DNA sequences. We use the experimentally supported data of the human genome to train the model, and perform experiments on human and other mammals, including mouse, cow and dog. The experimental results show that CrepHAN has more advantages on cross-species predictions, and outperforms the existing models by a large margin. Especially, for human-mouse cross-predictions, the area under the receiver operating characteristic (ROC) curve (AUC) score of ROC curve is increased by 0.033∼0.145 on the combined tissue dataset and 0.032∼0.109 on tissue-specific datasets. AVAILABILITY AND IMPLEMENTATION: bcmi.sjtu.edu.cn/∼yangyang/CrepHAN.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AraPPINet: An Updated Interactome for the Analysis of Hormone Signaling Crosstalk in Arabidopsis thaliana.

Protein-protein interactions (PPIs) play fundamental roles in various cellular processes. Here, we present a new version of computational interactome that contains more than 345,000 predicted PPIs involving about 51.2% of the Arabidopsis proteins. Compared to the earlier version, the updated AraPPINet displays a higher accuracy in predicting protein interactions through performance evaluation with independent datasets. In addition to the experimental verifications of the previous version, the new version has been subjected to further validation test that demonstrates its ability to discover novel PPIs involved in hormone signaling pathways. Moreover, network analysis shows that many overlapping proteins are significantly involved in the interactions which mediated the crosstalk among plant hormones. The new version of AraPPINet provides a more reliable interactome which would facilitate the understanding of crosstalk among hormone signaling pathways in plants.

It is possible that tumour-infiltrating granulocytes promote tumour progression.

Several lines of evidence indicate that tumour-infiltrating granulocytes (TIGs) promote tumour growth and progression. However, the prognostic significance of TIGs, the relationship between TIGs and Fas ligand (FasL) expressed on tumour cells remains unclear and warrants investigation. Using immunnostaining, we retrospectively investigated TIGs and FasL in 130 tissue specimens from gastric carcinoma. We analyzed the correlation among these markers, their association with clinicopathologic features and prognosis. The number of TIGs was significantly associated with FasL-expression (P=0.002). Further, TIGs were significantly associated with depth of tumour invasion, lymph node metastasis and tumour stage. Calculating the prognostic relevance, in multivariate analysis, TIGs [relative risk (RR)=1.014; 95% CI=1.002-1.027; P=0.015] and tumour stage were statistically significant factors for survival. Our results suggest that TIGs are conveniently measured by the immunostaining method, and possibly serve as an independent factor of prognosis in patients with gastric carcinoma. This is based on the fact that TIGs were significantly associated with tumour stage and shorter survival time.

The distribution and intracellular location of Fas and Fas Ligand following gastric carcinogenesis: Fas Ligand expressing gastric carcinoma cells can inhibit local immune response.

Previous reports indicated that Fas Ligand (FasL) in gastric carcinoma might support tumour cells to evade host immune attack. However, the mechanism induced by the Fas/FasL system has not yet been described on the basis of comparison of normal and malignant tissues in terms of the features of regional location of Fas and FasL. By using immunostaining methods, we studied the distribution and regional location of Fas and FasL in gastric epithelial cells (GECs), gastric carcinoma cells (GCCs), normal gastric stroma-infiltrating lymphoid cells (NGILs) and tumour-infiltrating lymphoid cells (TILs) in 59 tissue specimens of human gastric carcinoma. The expression of Fas within the entire GECs was higher than that in all GCCs (P < 0.0001); however, the expression of Fas in NGILs was lower than that in TILs (P < 0.0001). The expression of FasL showed no significant difference between GECs and GCCs, or between NGILs and TILs. When we analyzed the Fas/FasL expression on cytomembrane (CM) in GECs and GCCs, Fas-in-CM was detected in 79.4% and 33.33% (P < 0.05), compared with 3.03% and 56.67%, respectively, for FasL-in-CM (P < 0.001). Our results suggest that there is indeed a possible mechanism to assist cancer cells to evade host immune attack, and this mechanism depends on the dynamic state of Fas/FasL expression, that is, Fas showed a tendency to be expressed within the cells, whereas FasL showed a tendency to be expressed on the cell membrane following carcinogenesis.

[The observation of visual quality after the implantation of apodized diffractive multifocal intraocular lens].

OBJECTIVE: To obverse visual acuity, visual symptom and the rate of spectacle independence after implantation of a multifocal intraocular lens (MIOL) in patients with age related cataract. METHODS: Sixty patients (68 eyes) with age-related cataract were enrolled in two groups. ReSTOR SA60D3 MIOL and Natural SN60AT monofocal intraocular lens were specially implanted after phacoemulsification. Uncorrected distance visual acuity (UCDVA), best-corrected distance visual acuity (BCDVA), uncorrected near visual acuity (UCNVA), best-corrected near visual acuity (BCNVA), distance-corrected near vision acuity (DCNVA), visual symptom and the rate of spectacle independence were observed. RESULTS: UCDVA and BCDVA in multifocal group were not statistically different from those in monofocal group (P > 0.05). UCNVA and DCNVA were statistically better in multifocal group than in monofocal group (P < 0.05). The multifocal group has higher rate of spectacle independence than the monofocal group (73.3% versus 13.3%) (P < 0.05) when reading. The visual symptom such as glare and halo were more serious in multifocal group than in monofocal group (P < 0.05). CONCLUSIONS: Acrysof ReSTOR apodized diffractive multifocal intraocular lens may provide an excellent distance and near visual acuity, and decrease the dependence of spectacle.

[The clinical investigation of early visual function in cataract patients after implantation with aspheric intraocular lens].

PURPOSE: To initially evaluate the early visual function after implantation with aspheric intraocular lens METHODS: Eighty-eight subjects (91 eyes) were divided randomly into three groups: AcrySof IQ (SN60WF) group, KS-3Ai group and AcrySof Natural (SN60AT) group. Best corrected visual acuity was observed 1 day, 1 week and 1 month postoperatively, while contrast sensitivity and subjective vision were observed 1 month later. RESULTS: Best corrected visual acuity was obviously better in KS-3Ai group than in the other groups 1 day postoperatively (P < 0.05), but no significant difference was found 1 week and 1 month later among the groups (P > 0.05). When the pupil diameter was in 2.5 to 4.0 mm and 5.0 to 6.0 mm, AcrySof IQ and KS-3Ai groups were better than the AcrySof Natural group in the low and middle spatial frequency (P < 0.05). However, there was no significant difference between AcrySof IQ and KS-3Ai groups (P > 0.05). VF/QOL questionnaire was obtained, showing that implantation with AcrySof IQ and KS-3Ai satisfied patients preferably. CONCLUSIONS: Aspheric intraocular lens can greatly improve patients' contrast sensitivity and quality of vision.

Prognostic significance of immunohistochemically detected blood and lymphatic vessel invasion in colorectal carcinoma: its impact on prognosis.

BACKGROUND: The prognostic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) is unclear. Because of the absence of specific markers for venous and lymphatic vessels, earlier studies could not reliably distinguish between BVI and LVI. METHODS: By immunostaining for podoplanin and CD34 antigen, we retrospectively investigated LVI and BVI in 419 tissue specimens of colorectal carcinoma. We performed univariate and multivariate analysis of the clinicopathologic features, frequency of recurrence, and outcome of patients with or without LVI and BVI. RESULTS: The use of hematoxylin and eosin (H&E) staining to identify BVI and LVI yielded a false positive rate of 9.1% and false negative rate of 12.6%. The incidence of BVI was significantly higher among tumors with LVI than tumors without LVI (P <.001). In logistic multivariate analysis, only LVI (P < .001) was associated with lymph node metastasis and BVI (P = .015) was associated with distant recurrence. Calculating the prognostic relevance, both two invasion types correlated with decreased survival in univariate analysis (both P <.001). In multivariate analysis, BVI (P =.024), lymph node status (P =.003) and tumor stage (P <.001) remained statistically significant factors for survival. CONCLUSIONS: Our results suggest that immunohistologic evaluation of BVI and LVI could be useful in colorectal carcinoma indicating the risk of lymph node metastasis and recurrence, thereby contributing to prognostic evaluation.

Increased density and diameter of lymphatic microvessels correlate with lymph node metastasis in early stage invasive colorectal carcinoma.

To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.

Myofibroblasts correlate with lymphatic microvessel density and lymph node metastasis in early-stage invasive colorectal carcinoma.

BACKGROUND: Recent studies have shown that the interactions between tumor cells and stromal cells are important in tumor development. A possible correlation between tumor-activated myofibroblasts, the main component cells of tumor stroma, and lymphatic microvessel density (LMVD) or other clinical parameters in carcinoma was investigated. MATERIALS AND METHODS: Immunohistochemical examination of alpha-smooth muscle actin and podoplanin were performed in 83 cases of early-stage invasive colorectal carcinoma. RESULTS: There was a good correlation between proliferation of myofibroblasts (PMpt) and LMVD (LMVDpt) in the peri-tumoral area (p = 0.0034). Increased PMpt was also associated with lymphatic invasion (p = 0.0051) and with lymph node metastasis (p = 0.011). However, proliferation of myofibroblasts in intra-tumoral (PMit) areas was not associated with these clinical parameters. CONCLUSION: Proliferation of myofibroblasts in peri-tumoral areas seem to play an important role in lymphangiogenesis, and is also associated with lymph node metastasis.