Pandora: nucleotide-resolution bacterial pan-genomics with reference graphs

We present pandora, a novel pan-genome graph structure and algorithms for identifying variants across the full bacterial pan-genome. As much bacterial adaptability hinges on the accessory genome, methods which analyze SNPs in just the core genome have unsatisfactory limitations. Pandora approximates a sequenced genome as a recombinant of references, detects novel variation and pan-genotypes multiple samples. Using a reference graph of 578 Escherichia coli genomes, we compare 20 diverse isolates. Pandora recovers more rare SNPs than single-reference-based tools, is significantly better than picking the closest RefSeq reference, and provides a stable framework for analyzing diverse samples without reference bias.

Evaluation of Transmission Properties of Networks Described with Reference Graphs Using Unevenness Coefficients

This paper discusses an evaluation method of transmission properties of networks described with regular graphs (Reference Graphs) using unevenness coefficients. The first part of the paper offers generic information about describing network topology via graphs. The terms ‘chord graph’ and ‘Reference Graph’, which is a special form of a regular graph, are defined. The operating principle of a basic tool used for testing the network’s transmission properties is discussed. The next part consists of a description of the searching procedure of the shortest paths connecting any two nodes of a graph and the method determining the number of uses of individual graph edges. The analysis shows that using particular edges of a graph depends on two factors: their total number in minimum length paths and their total number in parallel paths connecting the graph nodes. The latter makes it possible to define an unevenness coefficient. The calculated values of the unevenness coefficients can be used to evaluate the transmission properties of networks and to control the distribution of transmission resources.

Designing Thin 2.5D Parts Optimized for Fused Deposition Modeling

This chapter builds new knowledge for design engineers adopting fused deposition modeling (FDM) technology as an end manufacturing process, rather than simply as a prototyping process. Based on research into 2.5D printing and its use in real-world additive manufacturing situations, a study featuring 111 test pieces across the range of 0.4-4.0mm in thickness were analyzed in increments of 0.1mm to understand how these attributes affect the quality and print time of the parts and isolate specific dimensions which are optimized for the FDM process. The results revealed optimized zones where the outer wall, inner wall/s, and/or infill are produced as continuous extrusions significantly faster to print than thicknesses falling outside of optimized zones. As a result, a quick reference graph and several equations are presented based on fundamental FDM principles, allowing design engineers to implement optimized wall dimensions in computer-aided design (CAD) rather than leaving print optimization to technicians and manufacturers in the final process parameters.

Demadroid: Object Reference Graph-Based Malware Detection in Android

Smartphone usage has been continuously increasing in recent years. In addition, Android devices are widely used in our daily life, becoming the most attractive target for hackers. Therefore, malware analysis of Android platform is in urgent demand. Static analysis and dynamic analysis methods are two classical approaches. However, they also have some drawbacks. Motivated by this, we present Demadroid, a framework to implement the detection of Android malware. We obtain the dynamic information to build Object Reference Graph and propose λ-VF2 algorithm for graph matching. Extensive experiments show that Demadroid can efficiently identify the malicious features of malware. Furthermore, the system can effectively resist obfuscated attacks and the variants of known malware to meet the demand for actual use.

Connectivity Problems on Heterogeneous Graphs

BackgroundNetwork connectivity problems are abundant in computational biology research, where graphs are used to represent a range of phenomena: from physical interactions between molecules to more abstract relationships such as gene co-expression. One common challenge in studying biological networks is the need to extract meaningful, small subgraphs out of large databases of potential interactions. A useful abstraction for this task turned out to be the Steiner network problems: given a reference “database” graph, find a parsimonious subgraph that satisfies a given set of connectivity demands. While this formulation proved useful in a number of instances, the next challenge is to account for the fact that the reference graph may not be static. This can happen for instance, when studying protein measurements in single cells or at different time points, whereby different subsets of conditions can have different protein milieu.Results and DiscussionWe introduce the condition Steiner network problem in which we concomitantly consider a set of distinct biological conditions. Each condition is associated with a set of connectivity demands, as well as a set of edges that are assumed to be present in that condition. The goal of this problem is to find a minimal subgraph that satisfies all the demands through paths that are present in the respective condition. We show that introducing multiple conditions as an additional factor makes this problem much harder to approximate. Specifically, we prove that for C conditions, this new problem is NP-hard to approximate to a factor of C – ϵ, for every C ≥ 2 and ϵ > 0, and that this bound is tight. Moving beyond the worst case, we explore a special set of instances where the reference graph grows monotonically between conditions, and show that this problem admits substantially improved approximation algorithms. We also developed an integer linear programming solver for the general problem and demonstrate its ability to reach optimality with instances from the human protein interaction network.ConclusionOur results demonstrate that in contrast to most connectivity problems studied in computational biology, accounting for multiplicity of biological conditions adds considerable complexity, which we propose to address with a new solver. Importantly, our results extend to several network connectivity problems that are commonly used in computational biology, such as Prize-Collecting Steiner Tree, and provide insight into the theoretical guarantees for their applications in a multiple condition setting.AvailabilityOur solver for the general condition Steiner network problem is available at https://github.com/YosefLab/condition_connectivity_problems

Graph Peak Caller: calling ChIP-Seq Peaks on Graph-based Reference Genomes

Graph-based representations are considered to be the future for reference genomes, as they allow integrated representation of the steadily increasing data on individual variation. Currently available tools allow de novo assembly of graph-based reference genomes, alignment of new read sets to the graph representation as well as certain analyses like variant calling and haplotyping. We here present a first method for calling ChIP-Seq peaks on read data aligned to a graph-based reference genome. The method is a graph generalization of the peak caller MACS2, and is implemented in an open source tool, Graph Peak Caller. By using the existing tool vg to build a pan-genome of Arabidopsis thaliana, we validate our approach by showing that Graph Peak Caller with a pan-genome reference graph can trace variants within peaks that are not part of the linear reference genome, and find peaks that in general are more motif-enriched than those found by MACS2.

Improved genome inference in the MHC using a population reference graph

In humans and many other species, while much is known about the extent and structure of genetic variation, such information is typically not used in assembling novel genomes. Rather, a single reference is used against which to map reads, which can lead to poor characterisation of regions of high sequence or structural diversity. Here, we introduce a population reference graph, which combines multiple reference sequences as well as catalogues of SNPs and short indels. The genomes of novel samples are reconstructed as paths through the graph using an efficient hidden Markov Model, allowing for recombination between different haplotypes and variants. By applying the method to the 4.5Mb extended MHC region on chromosome 6, combining eight assembled haplotypes, sequences of known classical HLA alleles and 87,640 SNP variants from the 1000 Genomes Project, we demonstrate, using simulations, SNP genotyping, short-read and longread data, how the method improves the accuracy of genome inference. Moreover, the analysis reveals regions where the current set of reference sequences is substantially incomplete, particularly within the Class II region, indicating the need for continued development of reference-quality genome sequences.