The EM Algorithm and the Rise of Computational Biology

In the past decade computational biology has grown from a cottage industry with a handful of researchers to an attractive interdisciplinary field, catching the attention and imagination of many quantitatively-minded scientists. Of interest to us is the key role played by the EM algorithm during this transformation. We survey the use of the EM algorithm in a few important computational biology problems surrounding the "central dogma"; of molecular biology: from DNA to RNA and then to proteins. Topics of this article include sequence motif discovery, protein sequence alignment, population genetics, evolutionary models and mRNA expression microarray data analysis.Comment: Published in at http://dx.doi.org/10.1214/09-STS312 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

A Survey of Word Reordering in Statistical Machine Translation: Computational Models and Language Phenomena

Word reordering is one of the most difficult aspects of statistical machine translation (SMT), and an important factor of its quality and efficiency. Despite the vast amount of research published to date, the interest of the community in this problem has not decreased, and no single method appears to be strongly dominant across language pairs. Instead, the choice of the optimal approach for a new translation task still seems to be mostly driven by empirical trials. To orientate the reader in this vast and complex research area, we present a comprehensive survey of word reordering viewed as a statistical modeling challenge and as a natural language phenomenon. The survey describes in detail how word reordering is modeled within different string-based and tree-based SMT frameworks and as a stand-alone task, including systematic overviews of the literature in advanced reordering modeling. We then question why some approaches are more successful than others in different language pairs. We argue that, besides measuring the amount of reordering, it is important to understand which kinds of reordering occur in a given language pair. To this end, we conduct a qualitative analysis of word reordering phenomena in a diverse sample of language pairs, based on a large collection of linguistic knowledge. Empirical results in the SMT literature are shown to support the hypothesis that a few linguistic facts can be very useful to anticipate the reordering characteristics of a language pair and to select the SMT framework that best suits them.Comment: 44 pages, to appear in Computational Linguistic

Inference of Markovian Properties of Molecular Sequences from NGS Data and Applications to Comparative Genomics

Next Generation Sequencing (NGS) technologies generate large amounts of short read data for many different organisms. The fact that NGS reads are generally short makes it challenging to assemble the reads and reconstruct the original genome sequence. For clustering genomes using such NGS data, word-count based alignment-free sequence comparison is a promising approach, but for this approach, the underlying expected word counts are essential. A plausible model for this underlying distribution of word counts is given through modelling the DNA sequence as a Markov chain (MC). For single long sequences, efficient statistics are available to estimate the order of MCs and the transition probability matrix for the sequences. As NGS data do not provide a single long sequence, inference methods on Markovian properties of sequences based on single long sequences cannot be directly used for NGS short read data. Here we derive a normal approximation for such word counts. We also show that the traditional Chi-square statistic has an approximate gamma distribution, using the Lander-Waterman model for physical mapping. We propose several methods to estimate the order of the MC based on NGS reads and evaluate them using simulations. We illustrate the applications of our results by clustering genomic sequences of several vertebrate and tree species based on NGS reads using alignment-free sequence dissimilarity measures. We find that the estimated order of the MC has a considerable effect on the clustering results, and that the clustering results that use a MC of the estimated order give a plausible clustering of the species.Comment: accepted by RECOMB-SEQ 201

MonoPerfCap: Human Performance Capture from Monocular Video

We present the first marker-less approach for temporally coherent 3D performance capture of a human with general clothing from monocular video. Our approach reconstructs articulated human skeleton motion as well as medium-scale non-rigid surface deformations in general scenes. Human performance capture is a challenging problem due to the large range of articulation, potentially fast motion, and considerable non-rigid deformations, even from multi-view data. Reconstruction from monocular video alone is drastically more challenging, since strong occlusions and the inherent depth ambiguity lead to a highly ill-posed reconstruction problem. We tackle these challenges by a novel approach that employs sparse 2D and 3D human pose detections from a convolutional neural network using a batch-based pose estimation strategy. Joint recovery of per-batch motion allows to resolve the ambiguities of the monocular reconstruction problem based on a low dimensional trajectory subspace. In addition, we propose refinement of the surface geometry based on fully automatically extracted silhouettes to enable medium-scale non-rigid alignment. We demonstrate state-of-the-art performance capture results that enable exciting applications such as video editing and free viewpoint video, previously infeasible from monocular video. Our qualitative and quantitative evaluation demonstrates that our approach significantly outperforms previous monocular methods in terms of accuracy, robustness and scene complexity that can be handled.Comment: Accepted to ACM TOG 2018, to be presented on SIGGRAPH 201