The Fast Heuristic Algorithms and Post-Processing Techniques to Design Large and Low-Cost Communication Networks

It is challenging to design large and low-cost communication networks. In this paper, we formulate this challenge as the prize-collecting Steiner Tree Problem (PCSTP). The objective is to minimize the costs of transmission routes and the disconnected monetary or informational profits. Initially, we note that the PCSTP is MAX SNP-hard. Then, we propose some post-processing techniques to improve suboptimal solutions to PCSTP. Based on these techniques, we propose two fast heuristic algorithms: the first one is a quasilinear time heuristic algorithm that is faster and consumes less memory than other algorithms; and the second one is an improvement of a stateof-the-art polynomial time heuristic algorithm that can find high-quality solutions at a speed that is only inferior to the first one. We demonstrate the competitiveness of our heuristic algorithms by comparing them with the state-of-the-art ones on the largest existing benchmark instances (169 800 vertices and 338 551 edges). Moreover, we generate new instances that are even larger (1 000 000 vertices and 10 000 000 edges) to further demonstrate their advantages in large networks. The state-ofthe-art algorithms are too slow to find high-quality solutions for instances of this size, whereas our new heuristic algorithms can do this in around 6 to 45s on a personal computer. Ultimately, we apply our post-processing techniques to update the bestknown solution for a notoriously difficult benchmark instance to show that they can improve near-optimal solutions to PCSTP. In conclusion, we demonstrate the usefulness of our heuristic algorithms and post-processing techniques for designing large and low-cost communication networks

The oligonucleotide frequency derived error gradient and its application to the binning of metagenome fragments

<p>Abstract</p> <p>Background</p> <p>The characterisation, or binning, of metagenome fragments is an important first step to further downstream analysis of microbial consortia. Here, we propose a one-dimensional signature, OFDEG, derived from the oligonucleotide frequency profile of a DNA sequence, and show that it is possible to obtain a meaningful phylogenetic signal for relatively short DNA sequences. The one-dimensional signal is essentially a compact representation of higher dimensional feature spaces of greater complexity and is intended to improve on the tetranucleotide frequency feature space preferred by current compositional binning methods.</p> <p>Results</p> <p>We compare the fidelity of OFDEG against tetranucleotide frequency in both an unsupervised and semi-supervised setting on simulated metagenome benchmark data. Four tests were conducted using assembler output of Arachne and phrap, and for each, performance was evaluated on contigs which are greater than or equal to 8 kbp in length and contigs which are composed of at least 10 reads. Using both G-C content in conjunction with OFDEG gave an average accuracy of 96.75% (semi-supervised) and 95.19% (unsupervised), versus 94.25% (semi-supervised) and 82.35% (unsupervised) for tetranucleotide frequency.</p> <p>Conclusion</p> <p>We have presented an observation of an alternative characteristic of DNA sequences. The proposed feature representation has proven to be more beneficial than the existing tetranucleotide frequency space to the metagenome binning problem. We do note, however, that our observation of OFDEG deserves further anlaysis and investigation. Unsupervised clustering revealed OFDEG related features performed better than standard tetranucleotide frequency in representing a relevant organism specific signal. Further improvement in binning accuracy is given by semi-supervised classification using OFDEG. The emphasis on a feature-driven, bottom-up approach to the problem of binning reveals promising avenues for future development of techniques to characterise short environmental sequences without bias toward cultivable organisms.</p

NAPA-VQ: Neighborhood Aware Prototype Augmentation with Vector Quantization for Continual Learning

Catastrophic forgetting; the loss of old knowledge upon acquiring new knowledge, is a pitfall faced by deep neural networks in real-world applications. Many prevailing solutions to this problem rely on storing exemplars (previously encountered data), which may not be feasible in applications with memory limitations or privacy constraints. Therefore, the recent focus has been on Non-Exemplar based Class Incremental Learning (NECIL) where a model incrementally learns about new classes without using any past exemplars. However, due to the lack of old data, NECIL methods struggle to discriminate between old and new classes causing their feature representations to overlap. We propose NAPA-VQ: Neighborhood Aware Prototype Augmentation with Vector Quantization, a framework that reduces this class overlap in NECIL. We draw inspiration from Neural Gas to learn the topological relationships in the feature space, identifying the neighboring classes that are most likely to get confused with each other. This neighborhood information is utilized to enforce strong separation between the neighboring classes as well as to generate old class representative prototypes that can better aid in obtaining a discriminative decision boundary between old and new classes. Our comprehensive experiments on CIFAR-100, TinyImageNet, and ImageNet-Subset demonstrate that NAPA-VQ outperforms the State-of-the-art NECIL methods by an average improvement of 5%, 2%, and 4% in accuracy and 10%, 3%, and 9% in forgetting respectively. Our code can be found in https://github.com/TamashaM/NAPA-VQ.git.Comment: Accepted to ICCV 202

The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways

BACKGROUND Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. RESULTS We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. CONCLUSIONS Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases

CoNVEX: Copy number variation estimation in exome sequencing data using HMM

Background One of the main types of genetic variations in cancer is Copy Number Variations (CNV). Whole exome sequenicng (WES) is a popular alternative to whole genome sequencing (WGS) to study disease specific genomic variations. However, finding CNV in Cancer samples using WES data has not been fully explored. Results We present a new method, called CoNVEX, to estimate copy number variation in whole exome sequencing data. It uses ratio of tumour and matched normal average read depths at each exonic region, to predict the copy gain or loss. The useful signal produced by WES data will be hindered by the intrinsic noise present in the data itself. This limits its capacity to be used as a highly reliable CNV detection source. Here, we propose a method that consists of discrete wavelet transform (DWT) to reduce noise. The identification of copy number gains/losses of each targeted region is performed by a Hidden Markov Model (HMM). Conclusion HMM is frequently used to identify CNV in data produced by various technologies including Array Comparative Genomic Hybridization (aCGH) and WGS. Here, we propose an HMM to detect CNV in cancer exome data. We used modified data from 1000 Genomes project to evaluate the performance of the proposed method. Using these data we have shown that CoNVEX outperforms the existing methods significantly in terms of precision. Overall, CoNVEX achieved a sensitivity of more than 92% and a precision of more than 50%

Genome classification by gene distribution: An overlapping subspace clustering approach

<p>Abstract</p> <p>Background</p> <p>Genomes of lower organisms have been observed with a large amount of horizontal gene transfers, which cause difficulties in their evolutionary study. Bacteriophage genomes are a typical example. One recent approach that addresses this problem is the unsupervised clustering of genomes based on gene order and genome position, which helps to reveal species relationships that may not be apparent from traditional phylogenetic methods.</p> <p>Results</p> <p>We propose the use of an overlapping subspace clustering algorithm for such genome classification problems. The advantage of subspace clustering over traditional clustering is that it can associate clusters with gene arrangement patterns, preserving genomic information in the clusters produced. Additionally, overlapping capability is desirable for the discovery of multiple conserved patterns within a single genome, such as those acquired from different species via horizontal gene transfers. The proposed method involves a novel strategy to vectorize genomes based on their gene distribution. A number of existing subspace clustering and biclustering algorithms were evaluated to identify the best framework upon which to develop our algorithm; we extended a generic subspace clustering algorithm called HARP to incorporate overlapping capability. The proposed algorithm was assessed and applied on bacteriophage genomes. The phage grouping results are consistent overall with the Phage Proteomic Tree and showed common genomic characteristics among the TP901-like, Sfi21-like and sk1-like phage groups. Among 441 phage genomes, we identified four significantly conserved distribution patterns structured by the terminase, portal, integrase, holin and lysin genes. We also observed a subgroup of Sfi21-like phages comprising a distinctive divergent genome organization and identified nine new phage members to the Sfi21-like genus: <it>Staphylococcus </it>71, phiPVL108, <it>Listeria </it>A118, 2389, <it>Lactobacillus phi </it>AT3, A2, <it>Clostridium </it>phi3626, <it>Geobacillus </it>GBSV1, and <it>Listeria monocytogenes </it>PSA.</p> <p>Conclusion</p> <p>The method described in this paper can assist evolutionary study through objectively classifying genomes based on their resemblance in gene order, gene content and gene positions. The method is suitable for application to genomes with high genetic exchange and various conserved gene arrangement, as demonstrated through our application on phages.</p

Positive-Unlabeled Learning for inferring drug interactions based on heterogeneous attributes

BACKGROUND: Investigating and understanding drug-drug interactions (DDIs) is important in improving the effectiveness of clinical care. DDIs can occur when two or more drugs are administered together. Experimentally based DDI detection methods require a large cost and time. Hence, there is a great interest in developing efficient and useful computational methods for inferring potential DDIs. Standard binary classifiers require both positives and negatives for training. In a DDI context, drug pairs that are known to interact can serve as positives for predictive methods. But, the negatives or drug pairs that have been confirmed to have no interaction are scarce. To address this lack of negatives, we introduce a Positive-Unlabeled Learning method for inferring potential DDIs. RESULTS: The proposed method consists of three steps: i) application of Growing Self Organizing Maps to infer negatives from the unlabeled dataset; ii) using a pairwise similarity function to quantify the overlap between individual features of drugs and iii) using support vector machine classifier for inferring DDIs. We obtained 6036 DDIs from DrugBank database. Using the proposed approach, we inferred 589 drug pairs that are likely to not interact with each other; these drug pairs are used as representative data for the negative class in binary classification for DDI prediction. Moreover, we classify the predicted DDIs as Cytochrome P450 (CYP) enzyme-Dependent and CYP-Independent interactions invoking their locations on the Growing Self Organizing Map, due to the particular importance of these enzymes in clinically significant interaction effects. Further, we provide a case study on three predicted CYP-Dependent DDIs to evaluate the clinical relevance of this study. CONCLUSION: Our proposed approach showed an absolute improvement in F1-score of 14 and 38% in comparison to the method that randomly selects unlabeled data points as likely negatives, depending on the choice of similarity function. We inferred 5300 possible CYP-Dependent DDIs and 592 CYP-Independent DDIs with the highest posterior probabilities. Our discoveries can be used to improve clinical care as well as the research outcomes of drug development

Unsupervised discovery of microbial population structure within metagenomes using nucleotide base composition

An approach to infer the unknown microbial population structure within a metagenome is to cluster nucleotide sequences based on common patterns in base composition, otherwise referred to as binning. When functional roles are assigned to the identified populations, a deeper understanding of microbial communities can be attained, more so than gene-centric approaches that explore overall functionality. In this study, we propose an unsupervised, model-based binning method with two clustering tiers, which uses a novel transformation of the oligonucleotide frequency-derived error gradient and GC content to generate coarse groups at the first tier of clustering; and tetranucleotide frequency to refine these groups at the secondary clustering tier. The proposed method has a demonstrated improvement over PhyloPythia, S-GSOM, TACOA and TaxSOM on all three benchmarks that were used for evaluation in this study. The proposed method is then applied to a pyrosequenced metagenomic library of mud volcano sediment sampled in southwestern Taiwan, with the inferred population structure validated against complementary sequencing of 16S ribosomal RNA marker genes. Finally, the proposed method was further validated against four publicly available metagenomes, including a highly complex Antarctic whale-fall bone sample, which was previously assumed to be too complex for binning prior to functional analysis

Gene functionality's influence on the second codon: A large-scale survey of second codon composition in three domains

AbstractThe second codon of a transcript, besides encoding for an amino acid, is now known to also have multiple molecular functions and is involved in translation efficiency and protein turn-over and maturation processing. These multiple purposes therefore make the selection constraints on this codon's composition more complex. To examine the biological significance of various permutations of the second codon, we conducted a systematic survey of second codon composition from 442 selected genomes across three domains. The amino acid bias of the second codon is associated with specific protein functions. The most common amino acids (S, A, K and T) are significantly avoided in Cell Envelope-related genes but preferred in Translation or Energy Metabolism-related genes, suggesting that the function of a gene product is a significant factor influencing the composition of the second codon