Current Bioinformatics - Volume 14, Issue 2, 2019

Background: Tuberculosis (TB) is still a major public health concern world-wide. The increasing global burden of TB is linked to HIV infection. HIV-TB coinfection has also conditioned clinical aspects of the TB. Since the HIV is beginning in the 1980s, the HIV infection poses a significant challenge in global TB control. Objective: In this review we focused on the challenges of epidemiological and clinical feature of tuberculosis presented by the HIV coinfection. Method: The article consists of a summary of the most important effects presented by the HIV coinfection on epidemiological and clinical feature of tuberculosis. The article analyzes and summary the causes for these challenges. Results: The major challenges to strategy of TB control and clinical feature of TB-HIV coinfection are presented in this paper. Conclusion: HIV/TB co-infection is synergic, interactive and reciprocal with significant impact. The infection of HIV and Mtb affect each other and the breakdown the immune function in TB/HIV coinfected individual. HIV infection has changed the strategy of TB control, however HIV increases global burden of TB, the reduction in the TB incidence rate is far from sufficient. Atypically clinical manifestations in TB/HIV co-infected patients and increased MDR-TB and XDR-TB contribute to the challenges in the diagnosis and treatment. Increased complexity of managing patients requires expertise in the clinical m knowledge. The focused efforts to control HIV-related TB are of great urgency. These findings will provide insight into the prevention, detection and treatment of tuberculosis and will guide advances towards tuberculosis control.

Background: There have been numerous experiments and studies on liver cancer by biomedical scientists, while no comprehensive and systematic exploration has yet been conducted. Therefore, this study aimed to systematically dissect the transcriptional and non-coding RNAmediated mechanisms of liver cancer dysfunction. Method: At first, we collected 974 liver cancer associated genes from the Online Mendelian Inheritance in Man (OMIM). Afterwards, their interactors were recruited from STRING database so as to identify 18 co-expression modules in liver cancer patient expression profile. Crosstalk analysis showed the interactive relationship between these modules. In addition, core drivers for modules were identified, including 111 transcription factors (STAT3, JUN and NFKB1, etc.) and 1492 ncRNAs (FENDRR and miR-340-5p, etc.). Results: In view of the results of enrichment, we found that these core drivers were significantly involved in Notch signaling, Wnt / β-catenin pathways, cell proliferation, apoptosis-related functions and pathways, suggesting they can affect the development of liver cancer. Furthermore, a global effect on bio-network associated with liver cancer has been integrated from the ncRNA and TF pivot network, module crosstalk network, module-function/pathways network. It involves various development and progression of cancer. Conclusion: Overall, our analysis further suggests that comprehensive network analysis will help us to not only understand in depth the molecular mechanisms, but also reveal the influence of related gene dysfunctional modules on the occurrence and progression of liver cancer. It provides a valuable reference for the design of liver cancer diagnosis and treatment.

Background: Dye-exclusion based cell viability analysis has been broadly used in cell biology including anticancer drug discovery studies. Viability analysis refers to the whole decision making process for the distinction of dead cells from live ones. Basically, cell culture samples are dyed with a special stain called trypan blue, so that the dead cells are selectively colored to darkish. This distinction provides critical information that may be used to expose influences of the studied drug on considering cell culture including cancer. Examiner’s experience and tiredness substantially affect the consistency throughout the manual observation of cell viability. The unsteady results of cell viability may end up with biased experimental results accordingly. Therefore, a machine learning based automated decision-making procedure is inevitably needed to improve consistency of the cell viability analysis. Objective: In this study, we investigate various combinations of classifiers and feature extractors (i.e. classification models) to maximize the performance of computer vision-based viability analysis. Method: The classification models are tested on novel hemocytometer image datasets which contain two types of cancer cell images, namely, caucasian promyelocytic leukemia (HL60), and chronic myelogenous leukemia (K562). Results: From the experimental results, k-Nearest Neighbor (KNN) and Random Forest (RF) by combining Local Phase Quantization (LPQ) achieve the lowest misclassification rates that are 0.031 and 0.082, respectively. Conclusion: The experimental results show that KNN and RF with LPQ can be powerful alternatives to the conventional manual cell viability analysis. Also, the collected datasets are released from the “biochem.atilim.edu.tr/datasets/” web address publically to academic studies.

Background: Self Interacting Proteins (SIPs) play an essential role in various aspects of the structural and functional organization of the cell. Objective: In the study, we presented a novelty sequence-based computational approach for predicting Self-interacting proteins using Weighed-Extreme Learning Machine (WELM) model combined with an Autocorrelation (AC) descriptor protein feature representation. Method: The major advantage of the proposed method mainly lies in adopting an effective feature extraction method to represent candidate self-interacting proteins by using the evolutionary information embedded in PSI-BLAST-constructed Position Specific Scoring Matrix (PSSM); and then employing a reliable and effective WELM classifier to perform classify. Result: In order to evaluate the performance, the proposed approach is applied to yeast and human SIP datasets. The experimental results show that our method obtained 93.43% and 98.15% prediction accuracies on yeast and human dataset, respectively. Extensive experiments are carried out to compare our approach with the SVM classifier and existing sequence-based method on yeast and human dataset. Experimental results show that the performance of our method is better than several other state-of-theart methods. Conclusion: It is demonstrated that the proposed method is suitable for SIPs detection and can execute incredibly well for identifying Sips. In order to facilitate extensive studies for future proteomics research, we developed a freely available web server called WELM-AC-SIPs in Hypertext Preprocessor (PHP) for predicting SIPs. The web server including source code and the datasets are available at http://219.219.62.123:8888/WELMAC/.

Background: Biological sequence data have increased at a rapid rate due to the advancements in sequencing technologies and reduction in the cost of sequencing data. The huge increase in these data presents significant research challenges to researchers. In addition to meaningful analysis, data storage is also a challenge, an increase in data production is outpacing the storage capacity. Data compression is used to reduce the size of data and thus reduces storage requirements as well as transmission cost over the internet. Objective: This article presents a novel compression algorithm (FCompress) for Next Generation Sequencing (NGS) data in FASTQ format. Method: The proposed algorithm uses bits manipulation and dictionary-based compression for bases compression. Headers are compressed with reference-based compression, whereas quality scores are compressed with Huffman coding. Results: The proposed algorithm is validated with experimental results on real datasets. The results are compared with both general purpose and specialized compression programs. Conclusion: The proposed algorithm produces better compression ratio in a comparable time to other algorithms.

Background: Accurate and exhaustive identification of genomic deletion events is the basis for understanding their roles in phenotype variation. Developing effective algorithms to identify deletions using next generation sequencing (NGS) data remains a challenge. Objective: The accurate and exhaustive identification of genomic deletion events is important; we present a new approach, Defind, to detect deletions using NGS data from a single sample mapped to the reference genome sequences. Method: The operating system(s) is Linux. Programming languages are Perl and R. We present Defind, a new approach for detecting medium- and large-sized deletions, based on inspecting the depth of coverage, GC content, mapping quality, and paired-end information of NGS data, simultaneously. We carried out detailed comparisons between Defind and other deletion detection methods using both simulation data and real data. Results: In simulation studies, Defind could retrieve more deletions than other methods at low to medium sequencing coverage (e.g., 5 to 10 with no false positives. Using real data, 94% of deletions commonly detected by at least two other methods were also detected by Defind. In addition, 90% of the deletions detected by Defind using the real data were positively supported by comparative genomic hybridization results, demonstrating the efficiency of Defind. Conclusion: Defind performed robustly at different sequence coverage with different read length in the simulation study. Our studies also provided a significant practical guidance to select appropriate methods to detect genomic deletions using NGS data.

Background: Lung cancer is a greatest threat to people's health and life. CT image leads to unclear boundary segmentation. Segmentation of irregular nodules and complex structure, boundary information is not well considered and lung nodules have always been a hot topic. Objective: In this study, the pulmonary nodule segmentation is accomplished with the new graph cut algorithm. The problem of segmenting the juxta-pleural and juxta-vascular nodules was investigated which is based on graph cut algorithm. Methods: Firstly, the inflection points by the curvature was decided. Secondly, we used kernel graph cut to segment the nodules for the initial edge. Thirdly, the seeds points based on cast raying method is performed; lastly, a novel geodesic distance function is proposed to improve the graph cut algorithm and applied in lung nodules segmentation. Results: The new algorithm has been tested on total 258 nodules. Table 1 summarizes the morphologic features of all the nodules and given the results between the successful segmentation group and the poor/failed segmentation group. Figure 1 to Fig. (12) shows segmentation effect of Juxta-vascular nodules, Juxta-pleural nodules, and comparted with the other interactive segmentation methods. Conclusion: The experimental verification shows better results with our algorithm, the results will measure the volume numerical approach to nodule volume. The results of lung nodules segmentation in this study are as good as the results obtained by the other methods.

Background: Specific combinations of Histone Modifications (HMs) contributing towards histone code hypothesis lead to various biological functions. HMs combinations have been utilized by various studies to divide the genome into different regions. These study regions have been classified as chromatin states. Mostly Hidden Markov Model (HMM) based techniques have been utilized for this purpose. In case of chromatin studies, data from Next Generation Sequencing (NGS) platforms is being used. Chromatin states based on histone modification combinatorics are annotated by mapping them to functional regions of the genome. The number of states being predicted so far by the HMM tools have been justified biologically till now. Objective: The present study aimed at providing a computational scheme to identify the underlying hidden states in the data under consideration. Methods: We proposed a computational scheme HCVS based on hierarchical clustering and visualization strategy in order to achieve the objective of study. Results: We tested our proposed scheme on a real data set of nine cell types comprising of nine chromatin marks. The approach successfully identified the state numbers for various possibilities. The results have been compared with one of the existing models as well which showed quite good correlation. Conclusion: The HCVS model not only helps in deciding the optimal state numbers for a particular data but it also justifies the results biologically thereby correlating the computational and biological aspects.

Background: One of the pivotal challenges in nowadays genomic research domain is the fast processing of voluminous data such as the ones engendered by high-throughput Next-Generation Sequencing technologies. On the other hand, BLAST (Basic Local Alignment Search Tool), a longestablished and renowned tool in Bioinformatics, has shown to be incredibly slow in this regard. Objective: To improve the performance of BLAST in the processing of voluminous data, we have applied a novel memory-aware technique to BLAST for faster parallel processing of voluminous data. Method: We have used a master-worker model for the processing of voluminous data alongside a memory-aware technique in which the master partitions the whole data in equal chunks, one chunk for each worker, and consequently each worker further splits and formats its allocated data chunk according to the size of its memory. Each worker searches every split data one-by-one through a list of queries. Results: We have chosen a list of queries with different lengths to run insensitive searches in a huge database called UniProtKB/TrEMBL. Our experiments show 20 percent improvement in performance when workers used our proposed memory-aware technique compared to when they were not memory aware. Comparatively, experiments show even higher performance improvement, approximately 50 percent, when we applied our memory-aware technique to mpiBLAST. Conclusion: We have shown that memory-awareness in formatting bulky database, when running BLAST, can improve performance significantly, while preventing unexpected crashes in low-memory environments. Even though distributed computing attempts to mitigate search time by partitioning and distributing database portions, our memory-aware technique alleviates negative effects of page-faults on performance.

Background: Various properties of Protein-Protein Interaction (PPI) network have been widely exploited to discover the topological organizing principle and the crucial function motifs involving specific biological pathway or disease process. The current motifs of PPI network are either detected by the topology-based coarse grain algorithms, i.e. community discovering, or depended on the limited-accessible protein annotation data derived precise algorithms. However, the identified network motifs are hardly compatible with the well-defined biological functions according to those two types of methods. Method: In this paper, we proposed a minimal protein loop finding method to explore the elementary structural motifs of human PPI network. Initially, an improved article exchange model was designed to search all the independent shortest protein loops of PPI network. Furthermore, Gene Ontology (GO) based function clustering analysis was implemented to identify the biological functions of the shortest protein loops. Additionally, the disease process associated shortest protein loops were considered as the potential drug targets. Result: Our proposed method presents the lowest computational complexity and the highest functional consistency, compared to the three other methods. The functional enrichment and clustering analysis for the identified minimal protein loops revealed the high correlation between the protein loops and the corresponding biological functions, particularly, statistical analysis presenting the protein loops with the length less than 4 is closely connected with some disease process, suggesting the potential drug target. Conclusion: Our minimal protein loop method provides a novel manner to precisely define the functional motif of PPI network, which extends the current knowledge about the cooperating mechanisms and topological properties of protein modules composed of the short loops.