The evolutionary history of a set of taxa is usually represented by a phylogenetic tree, and this model has greatly facilitated the discussion and testing of hypotheses. However, it is well known that more complex evolutionary scenarios are poorly described by such models. Further, even when evolution proceeds in a tree-like manner, analysis of the data may not be best served by using methods that enforce a tree structure but rather by a richer visualization of the data to evaluate its properties, at least as an essential first step. Thus, phylogenetic networks should be employed when reticulate events such as hybridization, horizontal gene transfer, recombination, or gene duplication and loss are believed to be involved, and, even in the absence of such events, phylogenetic networks have a useful role to play. This article reviews the terminology used for phylogenetic networks and covers both split networks and reticulate networks, how they are defined, and how they can be interpreted. Additionally, the article outlines the beginnings of a comprehensive statistical framework for applying split network methods. We show how split networks can represent confidence sets of trees and introduce a conservative statistical test for whether the conflicting signal in a network is treelike. Finally, this article describes a new program, SplitsTree4, an interactive and comprehensive tool for inferring different types of phylogenetic networks from sequences, distances, and trees.

https://bioinformatics.cs.vt.edu/~easychair/HusonBryant_MBE_2006.pdf

Application of Phylogenetic Networks in Evolutionary Studies

MEGAHIT is a NGS de novo assembler for assembling large and complex metagenomics data in a time- and cost-efficient manner. It finished assembling a soil metagenomics dataset with 252Gbps in 44.1 hours and 99.6 hours on a single computing node with and without a GPU, respectively. MEGAHIT assembles the data as a whole, i.e., it avoids pre-processing like partitioning and normalization, which might compromise on result integrity. MEGAHIT generates 3 times larger assembly, with longer contig N50 and average contig length than the previous assembly. 55.8% of the reads were aligned to the assembly, which is 4 times higher than the previous. The source code of MEGAHIT is freely available at this https URL under GPLv3 license.

MEGAHIT: An ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph

While genome assembly projects have been successful in many haploid and inbred species, the assembly of noninbred or rearranged heterozygous genomes remains a major challenge. To address this challenge, we introduce the open-source FALCON and FALCON-Unzip algorithms (https://github.com/PacificBiosciences/FALCON/) to assemble long-read sequencing data into highly accurate, contiguous, and correctly phased diploid genomes. We generate new reference sequences for heterozygous samples including an F1 hybrid of Arabidopsis thaliana, the widely cultivated Vitis vinifera cv. Cabernet Sauvignon, and the coral fungus Clavicorona pyxidata, samples that have challenged short-read assembly approaches. The FALCON-based assemblies are substantially more contiguous and complete than alternate short- or long-read approaches. The phased diploid assembly enabled the study of haplotype structure and heterozygosities between homologous chromosomes, including the identification of widespread heterozygous structural variation within coding sequences.

/pdf/phased-diploid-genome-assembly-with-single-molecule-real-1o4qqi287e.pdf

Phased diploid genome assembly with single-molecule real-time sequencing

Single-molecule sequencing instruments can generate multikilobase sequences with the potential to greatly improve genome and transcriptome assembly. However, the error rates of single-molecule reads are high, which has limited their use thus far to resequencing bacteria. To address this limitation, we introduce a correction algorithm and assembly strategy that uses short, high-fidelity sequences to correct the error in single-molecule sequences. We demonstrate the utility of this approach on reads generated by a PacBio RS instrument from phage, prokaryotic and eukaryotic whole genomes, including the previously unsequenced genome of the parrot Melopsittacus undulatus, as well as for RNA-Seq reads of the corn (Zea mays) transcriptome. Our long-read correction achieves >99.9% base-call accuracy, leading to substantially better assemblies than current sequencing strategies: in the best example, the median contig size was quintupled relative to high-coverage, second-generation assemblies. Greater gains are predicted if read lengths continue to increase, including the prospect of single-contig bacterial chromosome assembly.

/pdf/hybrid-error-correction-and-de-novo-assembly-of-single-31pice1h96.pdf

Hybrid error correction and de novo assembly of single-molecule sequencing reads

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell-MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory.

/pdf/the-neuronal-architecture-of-the-mushroom-body-provides-a-4jan707nqc.pdf

The neuronal architecture of the mushroom body provides a logic for associative learning

Expression.- Spectral Clustering Gene Ontology Terms to Group Genes by Function.- Dynamic De-Novo Prediction of microRNAs Associated with Cell Conditions: A Search Pruned by Expression.- Clustering Gene Expression Series with Prior Knowledge.- A Linear Time Biclustering Algorithm for Time Series Gene Expression Data.- Time-Window Analysis of Developmental Gene Expression Data with Multiple Genetic Backgrounds.- Phylogeny.- A Lookahead Branch-and-Bound Algorithm for the Maximum Quartet Consistency Problem.- Computing the Quartet Distance Between Trees of Arbitrary Degree.- Using Semi-definite Programming to Enhance Supertree Resolvability.- An Efficient Reduction from Constrained to Unconstrained Maximum Agreement Subtree.- Pattern Identification in Biogeography.- On the Complexity of Several Haplotyping Problems.- A Hidden Markov Technique for Haplotype Reconstruction.- Algorithms for Imperfect Phylogeny Haplotyping (IPPH) with a Single Homoplasy or Recombination Event.- Networks.- A Faster Algorithm for Detecting Network Motifs.- Reaction Motifs in Metabolic Networks.- Reconstructing Metabolic Networks Using Interval Analysis.- Genome Rearrangements.- A 1.375-Approximation Algorithm for Sorting by Transpositions.- A New Tight Upper Bound on the Transposition Distance.- Perfect Sorting by Reversals Is Not Always Difficult.- Minimum Recombination Histories by Branch and Bound.- Sequences.- A Unifying Framework for Seed Sensitivity and Its Application to Subset Seeds.- Generalized Planted (l,d)-Motif Problem with Negative Set.- Alignment of Tandem Repeats with Excision, Duplication, Substitution and Indels (EDSI).- The Peres-Shields Order Estimator for Fixed and Variable Length Markov Models with Applications to DNA Sequence Similarity.- Multiple Structural RNA Alignment with Lagrangian Relaxation.- Faster Algorithms for Optimal Multiple Sequence Alignment Based on Pairwise Comparisons.- Ortholog Clustering on a Multipartite Graph.- Linear Time Algorithm for Parsing RNA Secondary Structure.- A Compressed Format for Collections of Phylogenetic Trees and Improved Consensus Performance.- Structure.- Optimal Protein Threading by Cost-Splitting.- Efficient Parameterized Algorithm for Biopolymer Structure-Sequence Alignment.- Rotamer-Pair Energy Calculations Using a Trie Data Structure.- Improved Maintenance of Molecular Surfaces Using Dynamic Graph Connectivity.- The Main Structural Regularities of the Sandwich Proteins.- Discovery of Protein Substructures in EM Maps.

Algorithms in Bioinformatics: 5th International Workshop, WABI 2005, Mallorca, Spain, October 3-6, 2005, Proceedings (Lecture Notes in Computer Science / Lecture Notes in Bioinformatics)

Graph-theoretic models have come to the forefront as some of the most powerful and practical methods for sequence assembly. Simultaneously, the computational hardness of the underlying graph algorithms has remained open. Here we present two theoretical results about the complexity of these models for sequence assembly. In the first part, we show sequence assembly to be NP-hard under two different models: string graphs and de Bruijn graphs. Together with an earlier result on the NP-hardness of overlap graphs, this demonstrates that all of the popular graph-theoretic sequence assembly paradigms are NP-hard. In our second result, we give the first, to our knowledge, optimal polynomial time algorithm for genome assembly that explicitly models the double-strandedness of DNA. We solve the Chinese Postman Problem on bidirected graphs using bidirected flow techniques and show to how to use it to find the shortest doublestranded DNA sequence which contains a given set of k-long words. This algorithm has applications to sequencing by hybridization and short read assembly.

/pdf/computability-of-models-for-sequence-assembly-35basryaux.pdf

Computability of models for sequence assembly

http://home.penglab.com/papersall/docpdf/2013_CurrentBiology.pdf

Clonal Development and Organization of the Adult Drosophila Central Brain

Motivation: Digital reconstruction, or tracing, of 3D neuron structures is critical toward reverse engineering the wiring and functions of a brain. However, despite a number of existing studies, this task is still challenging, especially when a 3D microscopic image has low signal-to-noise ratio (SNR) and fragmented neuron segments. Published work can handle these hard situations only by introducing global prior information, such as where a neurite segment starts and terminates. However, manual incorporation of such global information can be very time consuming. Thus, a completely automatic approach for these hard situations is highly desirable.

Results: We have developed an automatic graph algorithm, called the all-path pruning (APP), to trace the 3D structure of a neuron. To avoid potential mis-tracing of some parts of a neuron, an APP first produces an initial over-reconstruction, by tracing the optimal geodesic shortest path from the seed location to every possible destination voxel/pixel location in the image. Since the initial reconstruction contains all the possible paths and thus could contain redundant structural components (SC), we simplify the entire reconstruction without compromising its connectedness by pruning the redundant structural elements, using a new maximal-covering minimal-redundant (MCMR) subgraph algorithm. We show that MCMR has a linear computational complexity and will converge. We examined the performance of our method using challenging 3D neuronal image datasets of model organisms (e.g. fruit fly).

Availability: The software is available upon request. We plan to eventually release the software as a plugin of the V3D-Neuron package at http://penglab.janelia.org/proj/v3d.

Contact: pengh@janelia.hhmi.org

/pdf/automatic-3d-neuron-tracing-using-all-path-pruning-4a2kszamlq.pdf

Automatic 3D neuron tracing using all-path pruning

ANREP is a system for finding matches to patterns composed of (i) spacing constraints called 'spacers', and (ii) approximate matches to 'motifs' that are, recursively, patterns composed of 'atomic' symbols. A user specifies such patterns via a declarative, free-format and strongly typed language called A that is presented here in a tutorial style through a series of progressively more complex examples. The sample patterns are for protein and DNA sequences, the application domain for which ANREP was specifically created. ANREP provides a unified framework for almost all previously proposed biosequence patterns and extends them by providing approximate matching, a feature heretofore unavailable except for the limited case of individual sequences. The performance of ANREP is discussed and an appendix gives a concise specification of syntax and semantics. A portable C software package implementing ANREP is available via anonymous remote file transfer.

/pdf/a-system-for-pattern-matching-applications-on-biosequences-cf2ba85m6g.pdf

Gene Myers

Papers

Algorithms in Bioinformatics: 5th International Workshop, WABI 2005, Mallorca, Spain, October 3-6, 2005, Proceedings (Lecture Notes in Computer Science / Lecture Notes in Bioinformatics)

Computability of models for sequence assembly

Clonal Development and Organization of the Adult Drosophila Central Brain

Automatic 3D neuron tracing using all-path pruning

A system for pattern matching applications on biosequences.