Advances in Bioinformatics最新文献

We tackle the problem of completing and inferring genetic networks under stationary conditions from static data, where network completion is to make the minimum amount of modifications to an initial network so that the completed network is most consistent with the expression data in which addition of edges and deletion of edges are basic modification operations. For this problem, we present a new method for network completion using dynamic programming and least-squares fitting. This method can find an optimal solution in polynomial time if the maximum indegree of the network is bounded by a constant. We evaluate the effectiveness of our method through computational experiments using synthetic data. Furthermore, we demonstrate that our proposed method can distinguish the differences between two types of genetic networks under stationary conditions from lung cancer and normal gene expression data.

Availability of complete plastid genomes of ten solanaceous species, Atropa belladonna, Capsicum annuum, Datura stramonium, Nicotiana sylvestris, Nicotiana tabacum, Nicotiana tomentosiformis, Nicotiana undulata, Solanum bulbocastanum, Solanum lycopersicum, and Solanum tuberosum provided us with an opportunity to conduct their in silico comparative analysis in depth. The size of complete chloroplast genomes and LSC and SSC regions of three species of Solanum is comparatively smaller than that of any other species studied till date (exception: SSC region of A. belladonna). AT content of coding regions was found to be less than noncoding regions. A duplicate copy of trnH gene in C. annuum and two alternative tRNA genes for proline in D. stramonium were observed for the first time in this analysis. Further, homology search revealed the presence of rps19 pseudogene and infA genes in A. belladonna and D. stramonium, a region identical to rps19 pseudogene in C. annum and orthologues of sprA gene in another six species. Among the eighteen intron-containing genes, 3 genes have two introns and 15 genes have one intron. The longest insertion was found in accD gene in C. annuum. Phylogenetic analysis using concatenated protein coding sequences gave two clades, one for Nicotiana species and another for Solanum, Capsicum, Atropa, and Datura.

K-ras is an oncogenic GTPase responsible for at least 15-25% of all non-small cell lung cancer cases worldwide. Lung cancer of both types is increasing with an alarming rate due to smoking habits in Malaysia among men and women. Natural products always offer alternate treatment therapies that are safe and effective. Typhonium flagelliforme or Keladi Tikus is a local plant known to possess anticancer properties. The whole extract is considered more potent than individual constituents. Since K-ras is the key protein in lung cancer, our aim was to identify the constituents of the plant that could target the mutated K-ras. Using docking strategies, reported potentially active compounds of Typhonium flagelliforme were docked into the allosteric surface pockets and switch regions of the K-ras protein to identify possible inhibitors. The selected ligands were found to have a high binding affinity for the switch II and the interphase region of the ras-SOS binding surface.

The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A). CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures.

This paper presents a hybrid method to extract endocardial contour of the right ventricular (RV) in 4-slices from 3D echocardiography dataset. The overall framework comprises four processing phases. In Phase I, the region of interest (ROI) is identified by estimating the cavity boundary. Speckle noise reduction and contrast enhancement were implemented in Phase II as preprocessing tasks. In Phase III, the RV cavity region was segmented by generating intensity threshold which was used for once for all frames. Finally, Phase IV is proposed to extract the RV endocardial contour in a complete cardiac cycle using a combination of shape-based contour detection and improved radial search algorithm. The proposed method was applied to 16 datasets of 3D echocardiography encompassing the RV in long-axis view. The accuracy of experimental results obtained by the proposed method was evaluated qualitatively and quantitatively. It has been done by comparing the segmentation results of RV cavity based on endocardial contour extraction with the ground truth. The comparative analysis results show that the proposed method performs efficiently in all datasets with overall performance of 95% and the root mean square distances (RMSD) measure in terms of mean ± SD was found to be 2.21 ± 0.35 mm for RV endocardial contours.

3D structures of proteins with coordinated Mn(2+) ions from bacteria with low, average, and high genomic GC-content have been analyzed (149 PDB files were used). Major Mn(2+) binders are aspartic acid (6.82% of Asp residues), histidine (14.76% of His residues), and glutamic acid (3.51% of Glu residues). We found out that the motif of secondary structure "beta strand-major binder-random coil" is overrepresented around all the three major Mn(2+) binders. That motif may be followed by either alpha helix or beta strand. Beta strands near Mn(2+) binding residues should be stable because they are enriched by such beta formers as valine and isoleucine, as well as by specific combinations of hydrophobic and hydrophilic amino acid residues characteristic to beta sheet. In the group of proteins from GC-rich bacteria glutamic acid residues situated in alpha helices frequently coordinate Mn(2+) ions, probably, because of the decrease of Lys usage under the influence of mutational GC-pressure. On the other hand, the percentage of Mn(2+) sites with at least one amino acid in the "beta strand-major binder-random coil" motif of secondary structure (77.88%) does not depend on genomic GC-content.

This paper proposes the use of ultrasonic microscale subarrayed MIMO RADARs to estimate the position of breast cancer nodes. The transmit and receive antenna arrays are divided into subarrays. In order to increase the signal diversity each subarray is assigned a different waveform from an orthogonal set. High-frequency ultrasonic transducers are used since a breast is considered to be a superficial structure. Closed form expressions for the optimal Neyman-Pearson detector are derived. The combination of the waveform diversity present in the subarrayed deployment and traditional phased-array RADAR techniques provides promising results.

Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of beta amyloid plaques (Aβ) which can induce neurite degeneration and progressive dementia. It has been identified that neuronal apoptosis is induced by binding of Aβ42 to pan neurotrophin receptor (p75NTR) and gave the possibility that beta amyloid oligomer is a ligand for p75NTR. However, the atomic contact point responsible for molecular interactions and conformational changes of the protein upon binding was not studied in detail. In view of this, we conducted a molecular docking and simulation study to investigate the binding behaviour of Aβ42 monomer with p75NTR ectodomain. Furthermore, we proposed a p75NTR-ectodomain-Aβ42 complex model. Our data revealed that, Aβ42 specifically recognizes CRD1 and CRD2 domains of the receptor and formed a "cap" like structure at the N-terminal of receptor which is stabilized by a network of hydrogen bonds. These findings are supported by molecular dynamics simulation that Aβ42 showed distinct structural alterations at N- and C-terminal regions due to the influence of the receptor binding site. Overall, the present study gives more structural insight on the molecular interactions of beta amyloid protein involved in the activation of p75NTR receptor.

Background. Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results. A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions. This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.

Diabetic retinopathy is the leading cause of blindness worldwide. It is caused by the abnormal growth of the retinal blood vessels. Plasminogen activator inhibitor1 (PAI1) is the key growth factor and the inhibition of PAI1 can reduce the angiogenesis. In this study, currently available inhibitors are taken and tested for the toxicity, binding affinity, and bioactivities of the compounds by in silico approach. Five toxic free inhibitors were identified, among which N-acetyl-D-glucosamine shows the significant binding affinity and two of the molecules are having the better bioactivity properties. The molecular optimization of 2-(acetylamino)-2-deoxy-A-D-glucopyranose and alpha-L-fucose can be used for the treatment of diabetic retinopathy.