A semi-screenshot to show the top page of the web-server iDNA-Prot|dis, which is available at http://bioinformatics.hitsz.edu.cn/iDNA-Prot_dis/.

<p>A semi-screenshot to show the top page of the web-server iDNA-Prot|dis, which is available at <a href="http://bioinformatics.hitsz.edu.cn/iDNA-Prot_dis/" target="_blank">http://bioinformatics.hitsz.edu.cn/iDNA-Prot_dis/</a>.</p

iDNA-Prot|dis: Identifying DNA-Binding Proteins by Incorporating Amino Acid Distance-Pairs and Reduced Alphabet Profile into the General Pseudo Amino Acid Composition

<div><p>Playing crucial roles in various cellular processes, such as recognition of specific nucleotide sequences, regulation of transcription, and regulation of gene expression, DNA-binding proteins are essential ingredients for both eukaryotic and prokaryotic proteomes. With the avalanche of protein sequences generated in the postgenomic age, it is a critical challenge to develop automated methods for accurate and rapidly identifying DNA-binding proteins based on their sequence information alone. Here, a novel predictor, called “iDNA-Prot|dis”, was established by incorporating the amino acid distance-pair coupling information and the amino acid reduced alphabet profile into the general pseudo amino acid composition (PseAAC) vector. The former can capture the characteristics of DNA-binding proteins so as to enhance its prediction quality, while the latter can reduce the dimension of PseAAC vector so as to speed up its prediction process. It was observed by the rigorous jackknife and independent dataset tests that the new predictor outperformed the existing predictors for the same purpose. As a user-friendly web-server, iDNA-Prot|dis is accessible to the public at <a href="http://bioinformatics.hitsz.edu.cn/iDNA-Prot_dis/" target="_blank">http://bioinformatics.hitsz.edu.cn/iDNA-Prot_dis/</a>. Moreover, for the convenience of the vast majority of experimental scientists, a step-by-step protocol guide is provided on how to use the web-server to get their desired results without the need to follow the complicated mathematic equations that are presented in this paper just for the integrity of its developing process. It is anticipated that the iDNA-Prot|dis predictor may become a useful high throughput tool for large-scale analysis of DNA-binding proteins, or at the very least, play a complementary role to the existing predictors in this regard.</p></div

An illustration for discriminant visualization and interpretation.

<p>(A) The discriminative power of the 400 amino acid pairs. Each element in this figure represents the sum score of the features with positive discriminant weights for a specific distance amino acid pair with <i>cp(20)</i>. The amino acids are identified by their one-letter code. The amino acids labelled by horizontal-axis and vertical-axis indicate the first amino acid and the second amino acid in the pairs, respectively. The adjacent colour bar shows the mapping of sum score values. (B) The different discriminant weights of distance amino acid pairs R-R. There are three kinds of features with positive discriminative power for amino acid pair R-R, including RR, R*R, and R**R with distance 1, 2, 3, respectively. (C) The occurrence distribution of RR, R*R, and R**R in the sequence of protein 1HLVA. The total occurrences of the three features are ten, which are shown in red dots. The two DNA-binding regions (sequence position 28–48, and 97–129) are shown in yellow colour. (D) The distribution of RR in the three dimensional structure of 1HLVA. Only one RR occurs outside of the two DNA-binding regions, which was shown in red square. (E) The distribution of R*R and R**R in the three dimensional structure of 1HLVA.</p

The ROC (receiver operating characteristic) curves obtained by different methods on the benchmark dataset using the jackknife tests.

<p>The areas under the ROC curves or AUC are 0.834, 0.826, 0.814, 0.815, 0.789 and 0.761 for iDNA-Prot|dis (cp(20)), iDNA-Prot|dis (cp(14)), DNAbinder (dimension 21), DNAbinder(dimension 400), DNA-Prot and iDNA-Prot, respectively. See the main text for further explanation.</p

The overall Acc values achieved by iDNA-Prot|dis for cp(20) with different <i>d</i> values based on the benchmark dataset through five-cross validation.

<p>The overall Acc values achieved by iDNA-Prot|dis for cp(20) with different <i>d</i> values based on the benchmark dataset through five-cross validation.</p

The jackknife test results by iDNA-Prot|dis with different amino acid alphabet profiles (cf. Eqs. 9–13) on the benchmark dataset of Eq. 1 (cf. Supporting Information S1).

a<p>The parameters used: <i>d</i> = 3, <i>C</i> = 4, .</p>b<p>The parameters used: <i>d</i> = 3, <i>C</i> = 4, .</p>c<p>The parameters used: <i>d</i> = 3, <i>C</i> = 2, .</p>d<p>The parameters used: <i>d</i> = 3, <i>C</i> = 64, .</p><p>The jackknife test results by iDNA-Prot|dis with different amino acid alphabet profiles (cf. Eqs. 9–13) on the benchmark dataset of Eq. 1 (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691.s001" target="_blank">Supporting Information S1</a>).</p

A comparison of the results^a obtained by iDNA-Prot|dis and the other methods on the independent dataset PDB186.

a<p>The results of iDNA-Prot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Lin1" target="_blank">[15]</a>, DNA-Prot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Kumar1" target="_blank">[14]</a>, DNAbinder <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Kumar2" target="_blank">[96]</a>, DNABIND <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Szilagyi1" target="_blank">[102]</a>, DNA-Threader <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Gao2" target="_blank">[5]</a>, and DBPPred <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Lou1" target="_blank">[97]</a> were obtained from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Lou1" target="_blank">[97]</a>.</p><p>A comparison of the results^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#nt110" target="_blank">a</a>} obtained by iDNA-Prot|dis and the other methods on the independent dataset PDB186.</p

A comparison of the jackknife test results by iDNA-Prot|dis with the other methods on the benchmark dataset of Eq. 1.

a<p>See the footnote c of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone-0106691-t001" target="_blank">Table 1</a>.</p>b<p>Results obtained by in-house implementation from DNAbinder <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Kumar2" target="_blank">[96]</a>.</p>c<p>Results obtained by in-house implementation from DNAbinder <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Kumar2" target="_blank">[96]</a>.</p>d<p>Results obtained by in-house implementation from DNA-Prot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Kumar1" target="_blank">[14]</a>.</p>e<p>Results obtained by in-house implementation from iDNA-Prot <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106691#pone.0106691-Lin1" target="_blank">[15]</a>.</p><p>A comparison of the jackknife test results by iDNA-Prot|dis with the other methods on the benchmark dataset of Eq. 1.</p

Identification of DNA-binding proteins by incorporating evolutionary information into pseudo amino acid composition via the top-n-gram approach

<div><p>DNA-binding proteins are crucial for various cellular processes and hence have become an important target for both basic research and drug development. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to establish an automated method for rapidly and accurately identifying DNA-binding proteins based on their sequence information alone. Owing to the fact that all biological species have developed beginning from a very limited number of ancestral species, it is important to take into account the evolutionary information in developing such a high-throughput tool. In view of this, a new predictor was proposed by incorporating the evolutionary information into the general form of pseudo amino acid composition via the top-n-gram approach. It was observed by comparing the new predictor with the existing methods via both jackknife test and independent data-set test that the new predictor outperformed its counterparts. It is anticipated that the new predictor may become a useful vehicle for identifying DNA-binding proteins. It has not escaped our notice that the novel approach to extract evolutionary information into the formulation of statistical samples can be used to identify many other protein attributes as well.</p></div

TLR3 Signaling in Macrophages Is Indispensable for the Protective Immunity of Invariant Natural Killer T Cells against Enterovirus 71 Infection

<div><p>Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT) cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial antiviral effector cells to protect young mice from EV71 infection before their adaptive immune systems were fully mature. EV71 infection led to activation of iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly, iNKT cell activation during EV71 infection required TLR3 signaling in macrophages, but not in dendritic cells (DCs). Mechanistically, interleukin (IL)-12 and endogenous CD1d-restricted antigens were both required for full activation of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral loads in central nervous system and more severe disease in EV71-infected mice. Altogether, our results suggest that iNKT cells may be involved in controlling EV71 infection in children when their adaptive immune systems are not fully developed, and also imply that iNKT cells might be an intervention target for treating EV71-infected patients.</p></div