41 research outputs found
BIGMAC : breaking inaccurate genomes and merging assembled contigs for long read metagenomic assembly.
BackgroundThe problem of de-novo assembly for metagenomes using only long reads is gaining attention. We study whether post-processing metagenomic assemblies with the original input long reads can result in quality improvement. Previous approaches have focused on pre-processing reads and optimizing assemblers. BIGMAC takes an alternative perspective to focus on the post-processing step.ResultsUsing both the assembled contigs and original long reads as input, BIGMAC first breaks the contigs at potentially mis-assembled locations and subsequently scaffolds contigs. Our experiments on metagenomes assembled from long reads show that BIGMAC can improve assembly quality by reducing the number of mis-assemblies while maintaining or increasing N50 and N75. Moreover, BIGMAC shows the largest N75 to number of mis-assemblies ratio on all tested datasets when compared to other post-processing tools.ConclusionsBIGMAC demonstrates the effectiveness of the post-processing approach in improving the quality of metagenomic assemblies
Alignment-free phylogenetic reconstruction: Sample complexity via a branching process analysis
We present an efficient phylogenetic reconstruction algorithm allowing
insertions and deletions which provably achieves a sequence-length requirement
(or sample complexity) growing polynomially in the number of taxa. Our
algorithm is distance-based, that is, it relies on pairwise sequence
comparisons. More importantly, our approach largely bypasses the difficult
problem of multiple sequence alignment.Comment: Published in at http://dx.doi.org/10.1214/12-AAP852 the Annals of
Applied Probability (http://www.imstat.org/aap/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Global Alignment of Molecular Sequences via Ancestral State Reconstruction
Molecular phylogenetic techniques do not generally account for such common
evolutionary events as site insertions and deletions (known as indels). Instead
tree building algorithms and ancestral state inference procedures typically
rely on substitution-only models of sequence evolution. In practice these
methods are extended beyond this simplified setting with the use of heuristics
that produce global alignments of the input sequences--an important problem
which has no rigorous model-based solution. In this paper we consider a new
version of the multiple sequence alignment in the context of stochastic indel
models. More precisely, we introduce the following {\em trace reconstruction
problem on a tree} (TRPT): a binary sequence is broadcast through a tree
channel where we allow substitutions, deletions, and insertions; we seek to
reconstruct the original sequence from the sequences received at the leaves of
the tree. We give a recursive procedure for this problem with strong
reconstruction guarantees at low mutation rates, providing also an alignment of
the sequences at the leaves of the tree. The TRPT problem without indels has
been studied in previous work (Mossel 2004, Daskalakis et al. 2006) as a
bootstrapping step towards obtaining optimal phylogenetic reconstruction
methods. The present work sets up a framework for extending these works to
evolutionary models with indels
SDT: a virus classification tool based on pairwise sequence alignment and identity calculation
The perpetually increasing rate at which viral full-genome sequences are being determined is creating a pressing demand for computational tools that will aid the objective classification of these genome sequences. Taxonomic classification approaches that are based on pairwise genetic identity measures are potentially highly automatable and are progressively gaining favour with the International Committee on Taxonomy of Viruses (ICTV). There are, however, various issues with the calculation of such measures that could potentially undermine the accuracy and consistency with which they can be applied to virus classification. Firstly, pairwise sequence identities computed based on multiple sequence alignments rather than on multiple independent pairwise alignments can lead to the deflation of identity scores with increasing dataset sizes. Also, when gap-characters need to be introduced during sequence alignments to account for insertions and deletions, methodological variations in the way that these characters are introduced and handled during pairwise genetic identity calculations can cause high degrees of inconsistency in the way that different methods classify the same sets of sequences. Here we present Sequence Demarcation Tool (SDT), a free user-friendly computer program that aims to provide a robust and highly reproducible means of objectively using pairwise genetic identity calculations to classify any set of nucleotide or amino acid sequences. SDT can produce publication quality pairwise identity plots and colour-coded distance matrices to further aid the classification of sequences according to ICTV approved taxonomic demarcation criteria. Besides a graphical interface version of the program for Windows computers, command-line versions of the program are available for a variety of different operating systems (including a parallel version for cluster computing platforms)
ThIEF: Finding Genome-wide Trajectories of Epigenetics Marks
We address the problem of comparing multiple genome-wide maps representing nucleosome positions or specific histone marks. These maps can originate from the comparative analysis of ChIP-Seq/MNase-Seq/FAIRE-Seq data for different cell types/tissues or multiple time points. The input to the problem is a set of maps, each of which is a list of genomics locations for nucleosomes or histone marks. The output is an alignment of nucleosomes/histone marks across time points (that we call trajectories), allowing small movements and gaps in some of the maps. We present a tool called ThIEF (TrackIng of Epigenetic Features) that can efficiently compute these trajectories. ThIEF comes into two "flavors": ThIEF:Iterative finds the trajectories progressively using bipartite matching, while ThIEF:LP solves a k-partite matching problem on a hyper graph using linear programming. ThIEF:LP is guaranteed to find the optimal solution, but it is slower than ThIEF:Iterative. We demonstrate the utility of ThIEF by providing an example of applications on the analysis of temporal nucleosome maps for the human malaria parasite. As a surprisingly remarkable result, we show that the output of ThIEF can be used to produce a supervised classifier that can accurately predict the position of stable nucleosomes (i.e., nucleosomes present in all time points) and unstable nucleosomes (i.e., present in at most half of the time points) from the primary DNA sequence. To the best of our knowledge, this is the first result on the prediction of the dynamics of nucleosomes solely based on their DNA binding preference. Software is available at https://github.com/ucrbioinfo/ThIEF
Un enfoque Multi-Objetivo a la optimización del Alineamiento Múltiple de Secuencias (MSA)
Multiple Sequence Alignment (MSA) is one of the main topics in the bioinformatics domain, consists in finding an optimal alignment for three or more biological sequences with the number maximum of conserved zones or totally aligned columns. Different scores to assess the quality of the alignments have been proposed, so the problem can be formulated and resolved as a Multi-Objective Optimization Problem (MOP). For this reason we have carried out a perfomanced study resolving the MSA problem under a multi-objective approach, considering two popular metrics as objectives to be optimized: The weighted Sum-Of-Pairs with affine gap penalties (wSOP) and the Totally Aligned Columns (TC), with three algorithms from the state-of- the-art of Multi-Objective Optimization: NSGAII, SPEA2 and MOCell. Our experiments reveals that the classic metaheuristic NSGA-II provides the best overall performance resolving some problems provided by the benchmark BAliBASE (v3.0), under a multi-objective and biological approach
An exact mathematical programming approach to multiple RNA sequence-structure alignment
One of the main tasks in computational biology is the computation of
alignments of genomic sequences to reveal their commonalities. In case of DNA
or protein sequences, sequence information alone is usually sufficient to
compute reliable alignments. RNA molecules, however, build spatial
conformations—the secondary structure—that are more conserved than the actual
sequence. Hence, computing reliable alignments of RNA molecules has to take
into account the secondary structure. We present a novel framework for the
computation of exact multiple sequence-structure alignments: We give a graph-
theoretic representation of the sequence-structure alignment problem and
phrase it as an integer linear program. We identify a class of constraints
that make the problem easier to solve and relax the original integer linear
program in a Lagrangian manner. Experiments on a recently published benchmark
show that our algorithms has a comparable performance than more costly dynamic
programming algorithms, and outperforms all other approaches in terms of
solution quality with an increasing number of input sequences
Looking for the Last Universal Common Ancestor (LUCA)
Genomic sequences across diverse species seem to align towards a common ancestry, eventually implying that eons ago some universal antecedent organism would have lived on the face of Earth. However, when evolution is understood not only as a biological process but as a general thermodynamic process, it becomes apparent that the quest for the last universal common ancestor is unattainable. Ambiguities in alignments are unavoidable because the driving forces and paths of evolution cannot be separated from each other. Thus tracking down life’s origin is by its nature a non-computable task. The thermodynamic tenet clarifies that evolution is a path-dependent process of least-time consumption of free energy. The natural process is without a demarcation line between animate and inanimate.Peer reviewe