iProEP: A Computational Predictor for Predicting Promoter.

Promoter is a fundamental DNA element located around the transcription start site (TSS) and could regulate gene transcription. Promoter recognition is of great significance in determining transcription units, studying gene structure, analyzing gene regulation mechanisms, and annotating gene functional information. Many models have already been proposed to predict promoters. However, the performances of these methods still need to be improved. In this work, we combined pseudo k-tuple nucleotide composition (PseKNC) with position-correlation scoring function (PCSF) to formulate promoter sequences of Homo sapiens (H. sapiens), Drosophila melanogaster (D. melanogaster), Caenorhabditis elegans (C. elegans), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli). Minimum Redundancy Maximum Relevance (mRMR) algorithm and increment feature selection strategy were then adopted to find out optimal feature subsets. Support vector machine (SVM) was used to distinguish between promoters and non-promoters. In the 10-fold cross-validation test, accuracies of 93.3%, 93.9%, 95.7%, 95.2%, and 93.1% were obtained for H. sapiens, D. melanogaster, C. elegans, B. subtilis, and E. coli, with the areas under receiver operating curves (AUCs) of 0.974, 0.975, 0.981, 0.988, and 0.976, respectively. Comparative results demonstrated that our method outperforms existing methods for identifying promoters. An online web server was established that can be freely accessed (http://lin-group.cn/server/iProEP/).

iLoc-lncRNA: predict the subcellular location of lncRNAs by incorporating octamer composition into general PseKNC.

Motivation: Long non-coding RNAs (lncRNAs) are a class of RNA molecules with more than 200 nucleotides. They have important functions in cell development and metabolism, such as genetic markers, genome rearrangements, chromatin modifications, cell cycle regulation, transcription and translation. Their functions are generally closely related to their localization in the cell. Therefore, knowledge about their subcellular locations can provide very useful clues or preliminary insight into their biological functions. Although biochemical experiments could determine the localization of lncRNAs in a cell, they are both time-consuming and expensive. Therefore, it is highly desirable to develop bioinformatics tools for fast and effective identification of their subcellular locations. Results: We developed a sequence-based bioinformatics tool called 'iLoc-lncRNA' to predict the subcellular locations of LncRNAs by incorporating the 8-tuple nucleotide features into the general PseKNC (Pseudo K-tuple Nucleotide Composition) via the binomial distribution approach. Rigorous jackknife tests have shown that the overall accuracy achieved by the new predictor on a stringent benchmark dataset is 86.72%, which is over 20% higher than that by the existing state-of-the-art predictor evaluated on the same tests. Availability and implementation: A user-friendly webserver has been established at http://lin-group.cn/server/iLoc-LncRNA, by which users can easily obtain their desired results. Supplementary information: Supplementary data are available at Bioinformatics online.

IonchanPred 2.0: A Tool to Predict Ion Channels and Their Types.

Ion channels (IC) are ion-permeable protein pores located in the lipid membranes of all cells. Different ion channels have unique functions in different biological processes. Due to the rapid development of high-throughput mass spectrometry, proteomic data are rapidly accumulating and provide us an opportunity to systematically investigate and predict ion channels and their types. In this paper, we constructed a support vector machine (SVM)-based model to quickly predict ion channels and their types. By considering the residue sequence information and their physicochemical properties, a novel feature-extracted method which combined dipeptide composition with the physicochemical correlation between two residues was employed. A feature selection strategy was used to improve the performance of the model. Comparison results of in jackknife cross-validation demonstrated that our method was superior to other methods for predicting ion channels and their types. Based on the model, we built a web server called IonchanPred which can be freely accessed from http://lin.uestc.edu.cn/server/IonchanPredv2.0.

Recent Advances in Conotoxin Classification by Using Machine Learning Methods.

Conotoxins are disulfide-rich small peptides, which are invaluable peptides that target ion channel and neuronal receptors. Conotoxins have been demonstrated as potent pharmaceuticals in the treatment of a series of diseases, such as Alzheimer's disease, Parkinson's disease, and epilepsy. In addition, conotoxins are also ideal molecular templates for the development of new drug lead compounds and play important roles in neurobiological research as well. Thus, the accurate identification of conotoxin types will provide key clues for the biological research and clinical medicine. Generally, conotoxin types are confirmed when their sequence, structure, and function are experimentally validated. However, it is time-consuming and costly to acquire the structure and function information by using biochemical experiments. Therefore, it is important to develop computational tools for efficiently and effectively recognizing conotoxin types based on sequence information. In this work, we reviewed the current progress in computational identification of conotoxins in the following aspects: (i) construction of benchmark dataset; (ii) strategies for extracting sequence features; (iii) feature selection techniques; (iv) machine learning methods for classifying conotoxins; (v) the results obtained by these methods and the published tools; and (vi) future perspectives on conotoxin classification. The paper provides the basis for in-depth study of conotoxins and drug therapy research.

Pro54DB: a database for experimentally verified sigma-54 promoters.

Summary: In prokaryotes, the σ54 promoters are unique regulatory elements and have attracted much attention because they are in charge of the transcription of carbon and nitrogen-related genes and participate in numerous ancillary processes and environmental responses. All findings on σ54 promoters are favorable for a better understanding of their regulatory mechanisms in gene transcription and an accurate discovery of genes missed by the wet experimental evidences. In order to provide an up-to-date, interactive and extensible database for σ54 promoter, a free and easy accessed database called Pro54DB (σ54 promoter database) was built to collect information of σ54 promoter. In the current version, it has stored 210 experimental-confirmed σ54 promoters with 297 regulated genes in 43 species manually extracted from 133 publications, which is helpful for researchers in fields of bioinformatics and molecular biology. Availability and Implementation: Pro54DB is freely available on the web at http://lin.uestc.edu.cn/database/pro54db with all major browsers supported. Contacts: greatchen@ncst.edu.cn or hlin@uestc.edu.cn

Prediction of cell-penetrating peptides with feature selection techniques.

Cell-penetrating peptides are a group of peptides which can transport different types of cargo molecules such as drugs across plasma membrane and have been applied in the treatment of various diseases. Thus, the accurate prediction of cell-penetrating peptides with bioinformatics methods will accelerate the development of drug delivery systems. The study aims to develop a powerful model to accurately identify cell-penetrating peptides. At first, the peptides were translated into a set of vectors with the same dimension by using dipeptide compositions. Secondly, the Analysis of Variance-based technique was used to reduce the dimension of the vector and explore the optimized features. Finally, the support vector machine was utilized to discriminate cell-penetrating peptides from non-cell-penetrating peptides. The five-fold cross-validated results showed that our proposed method could achieve an overall prediction accuracy of 83.6%. Based on the proposed model, we constructed a free webserver called C2Pred (http://lin.uestc.edu.cn/server/C2Pred).

Natural protein sequences are more intrinsically disordered than random sequences.

Most natural protein sequences have resulted from millions or even billions of years of evolution. How they differ from random sequences is not fully understood. Previous computational and experimental studies of random proteins generated from noncoding regions yielded inclusive results due to species-dependent codon biases and GC contents. Here, we approach this problem by investigating 10,000 sequences randomized at the amino acid level. Using well-established predictors for protein intrinsic disorder, we found that natural sequences have more long disordered regions than random sequences, even when random and natural sequences have the same overall composition of amino acid residues. We also showed that random sequences are as structured as natural sequences according to contents and length distributions of predicted secondary structure, although the structures from random sequences may be in a molten globular-like state, according to molecular dynamics simulations. The bias of natural sequences toward more intrinsic disorder suggests that natural sequences are created and evolved to avoid protein aggregation and increase functional diversity.

Interaction network analysis revealed biomarkers in myocardial infarction.

Myocardial infarction (MI) is a serious heart disease. The cardiac cells of patients with MI will die due to lack of blood for a long time. In this study, we aimed to find new targets for MI diagnosis and therapy. We downloaded GSE22229 including 12 blood samples from healthy persons and GSE29111 from Gene Expression Omnibus including 36 blood samples from MI patients. Then we identified differentially expressed genes (DEGs) in patients with MI compared to normal controls with p value < 0.05 and |logFC| > 1. Furthermore, interaction network and sub-network of these of these DEGs were constructed by NetBox. Linker genes were screened in the Global Network database. The degree of linker genes were calculated by igraph package in R language. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis were performed for DEGs and network modules. A total of 246 DEGs were identified in MI, which were enriched in the immune response. In the interaction network, LCK, CD247, CD3D, FYN, HLA-DRA, IL2, CD8A CD3E, CD4, CD3G had high degree, among which CD3E, CD4, CD3G were DEGs while others were linker genes screened from Global Network database. Genes in the sub-network were also enriched in the immune response pathway. The genes with high degree may be biomarkers for MI diagnosis and therapy.

Fluorescent nanoparticles for observing primo vascular system along sciatic nerve.

The primo vascular system was found in the epineurium along the rat sciatic nerve following subcutaneous injection of fluorescent nanoparticles at the Zusanli acupoint (ST-36). Nanoparticles were injected into the primo-vessel near ST-36 and flowed along the sciatic nerve. Fluorescence revealed a structure in the epineurium that was hardly detectable. Images of the isolated sample stained with 4',6-diamidino-2-phenylindole were captured using confocal microscopy. These images showed the distinctive nuclei distribution and multi-lumen structure of primo-vessels that differentiate them from lymphatic vessels, blood capillaries and nerves. This study demonstrates a new use for nanoparticles in fluorescence reflectance imaging techniques during in vivo imaging of primo-vessels.

Effect of parenteral and early intrajejunal nutrition on pancreatic digestive enzyme synthesis, storage and discharge in dog models of acute pancreatitis.

AIM: To study the effect of early intrajejunal nutrition on enzyme-protein synthesis and secretion during acute pancreatitis. METHODS: Fifteen dogs were randomly divided into parenteral nutrition (n = 7) and early intrajejunal nutrition groups (n = 8). An acute pancreatitis model was induced by injecting 5% sodium taurocholate and trypsin into the pancreas via the pancreatic duct. Intrajejunal nutrition was delivered with a catheter via a jejunostomy tube after the model was established for 24 h. On d 1 and 7 and at the beginning of nutritional support, radioactive tracing and electron microscopes were used to evaluate the enzyme-protein synthesis in acinar cells, the subcellular fractionation and the change in zymogen granules after 1.85 x 10(6) Bq L-(3)H phenylalanine was infused at 30, 60, 120, and 180 min. RESULTS: The 3H radioactivity in pancreatic acinar cells reached its peak level at 60 min, and the contents in the early intrajejunal nutrition group were higher than those in the parenteral nutrition group, which were then decreased. The mean number and area of zymogen granules did not show any significant statistical difference in both groups on d 1 or on d 7 (P > 0.05). CONCLUSION: Early intrajejunal nutrition might be effective in dogs with acute pancreatitis.

Effect of parenteral and enteral nutrition combined with octreotide on pancreatic exocrine secretion of patients with pancreatic fistula.

AIM: To evaluate the effect of parenteral and enteral nutrition combined with octreotide on pancreatic exocrine secretion of the patients with pancreatic fistula. METHODS: Pancreatic juice, drained directly from the pancreatic fistula, was collected, and the volume, protein, amylase, HCO(3)(-), K(+), Na(+) and Cl(-) were determined on d 1, 4 and 7 before and after 7-d treatment with octreotide, respectively. RESULTS: No differences in exocrine pancreatic secretion were observed during the enteral and parenteral nutrition period (t = 2.03, P > 0.05); there were significant decreases in pancreatic juice secretion volume, protein, amylase, HCO(3)(-), K(+), Na(+) and Cl(-) after parenteral and enteral nutrition combined with octreotide compared with octreotide pretreatment (t = 4.14, P < 0.05). CONCLUSION: There is no stimulatory effect on the pancreatic secretion by intrajejunal nutrition and parenteral nutrition. Octreotide is effective on the reduction of pancreatic fistula output.

Parenteral versus early intrajejunal nutrition: effect on pancreatitic natural course, entero-hormones release and its efficacy on dogs with acute pancreatitis.

AIM: To evaluate the effect of early intrajejunal nutrition (EIN) on the natural course, entero-hormone secretion and its efficacy on dogs with acute pancreatitis. METHODS: An acute pancreatitis model was induced by injecting 1 ml/kg of combined solution (2.5% sodium taurocholate and 8,000-10,000 BAEE units trypsin/ml) into the pancreas via pancreatic duct. Fifteen dogs were divided into parenteral nutrition (PN) group and EIN group. Two groups were isonitrogenous and isocaloric. EIN was used at postoperative 24 h. Serum glucose, calcium, amylase and lysosomal enzymes were determined before and 1, 4, 7 d after acute pancreatitis was induced. All the dogs were injected 50 uCi 125I-BSA 4 h before sacrificed on the 7th day. The 125I -BSA index of the pancreas/muscle, pancreas/blood, and pancreas pathology score (PPS) were determined. The peripheral plasma cholecystokinin (CCK), secretin (SEC) and gastrin were measured by ELISA and RIA, and was quantitative analysis of pancreatic juice and amylase, pancreatolipase and HCO3-, Cl-, Na+ and K+ performed by an autochemical analyzer at 30, 60, 120 and 180 min after beginning PN or EIN on the first day. RESULTS: There was no difference between two groups in the contents of serum calcium, amylase and lysosomal enzymes, 125I-BSA index of pancreas/muscle and pancreas/blood and PPS. The contents of CCK and gastrin in EIN were higher than those in PN group at 60 and 120 min (P<0.05). The content of SEC post-infusion of nutrition solution was higher than that of pre-infusion of nutrition solution in both groups, and only at 60 min SEC in EIN group was higher than that in PN group. The content of gastrin in EIN was higher than that in PN group at 120 and 180 min (P<0.05). The changes of pancreatic juice, amylase, pancreatolipase and HCO3-, Cl-, Na+ and K+ between two groups did not reach significantly statistical difference (P>0.05). CONCLUSION: EIN does not stimulate entero-hormone and pancreatic juice secretion, and enzyme-protein synthesis and release. EIN has no effect on the natural course of acute pancreatitis.

[Effects of enteral nutrition on uptake of amino acid and enzyme-protein synthesis of pancreatic acinar cell in acute pancreatic dogs].

OBJECTIVE: To evaluate the effect of intrajejunal nutrition on uptake of amino acid and enzyme-protein synthesis in pancreatic acinar cell and subcellular fractionation and zymogen granules in dogs with acute pancreatitis. METHODS: Fifteen dogs were induced acute pancreatitis by retrograde injection of 5% sodium-taurocholate into the pancreatic duct. Radioactive tracing and electron microscope were used to evaluate the change of amino acid uptake, enzyme-protein synthesis in acinar cell, subcellular fractionation, the quantitative analysis of mean zymogen granule number and mean zymogen granule area after injection L-(3)H-phenylalanine 30, 60, 120 1nd 180 min on the 7(th) day. RESULTS: The radioactivity of L-(3)H phenylalanine uptake by pancreatic acinar cells and incorporations of L-(3)H phenylalanine into newly synthesized enzyme-protein peaked at 60 min. In enteral nutrition (EN) group it was higher that that in parenteral nutrition (PN) group (P < 0.05), and then gradually declined. The radioactivity peaked at 60 min in zymogen granule, lysosomal-mitochondria and microsomal subcellular fractionation. The latter two decreased, bat there was no significant difference (P > 0.05). The change of the mean number and mean area of zymogen granules were not significant different between the EN group and PN group (P > 0.05). CONCLUSION: EN or PN do not stimulate pancreatic acinar uptake amino acid and enzyme-protein synthesis in acinar cell and subcellular fractionation.

Early intrajejunal nutrition: bacterial translocation and gut barrier function of severe acute pancreatitis in dogs.

OBJECTIVE: To evaluate the effect of early intrajejunal nutrition in attenuating bacterial and/or endotoxin translocation and improving gut barrier function of severe acute pancreatitis (SAP) in dogs. METHODS: 15 dogs were divided into parenteral nutrition (PN) group (7 dogs) and early intrajejunal nutrition (EIN) group (8). EIN was delivered nutrients via a needle jejunostomy catheter feeding at 48 h after operation. SAP model was induced by injecting 1 ml/kg of combined solution of 5% sodium taurocholate and 8000-10 000 BAEE units trypsin/ml into the pancreas via the pancreatic duct. Systemic blood samples were obtained before and 1, 3, 5, 7 d following SAP, and cultured by aerobic as well as anaerobic bacterial growth. Systemic plasma and portal vein endotoxin levels were quantified by the chromogenic limulus amebocyte lysate (LAL) technique. Portal vein blood and specimens of tissue from the mesenteriolum and mesocolon lymph nodes, lung, pulmonary portal lymph nodes, pancreatitistissue and periopancreas tissue were adopted before the experiment was finished. Aliquots of the homogenata were cultured as blood mentioned above to determine the magnitude of the bacteria. DNA, protein and the villi, the thickness of mucosa, and the whole bowel wall of the ileum and transverse colon were measured. RESULTS: The study showed that the levels of systemic plasma endotoxin and the magnitude of bacterial translocation to the portal and systemic blood and distant organ were reduced significantly in the EIN group as compared with the TPN group. The contents of Protein and DNA, the height of villi, the thickness of mucosa and whole bowel wall of the ileum and transverse colon in the EIN group were higher than those in the PN group. CONCLUSION: Our results suggested that EIN is safe and effective to be adopted by intrajejunal delivery of nutrients in SAP, decreases the occurrence of gut bacterial translocation, and improves the gut barrier function.