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

New topic detection in microblogs and topic model evaluation using topical alignment

textThis thesis deals with topic model evaluation and new topic detection in microblogs. Microblogs are short and thus may not carry any contextual clues. Hence it becomes challenging to apply traditional natural language processing algorithms on such data. Graphical models have been traditionally used for topic discovery and text clustering on sets of text-based documents. Their unsupervised nature allows topic models to be trained easily on datasets meant for specific domains. However the advantage of not requiring annotated data comes with a drawback with respect to evaluation difficulties. The problem aggravates when the data comprises microblogs which are unstructured and noisy. We demonstrate the application of three types of such models to microblogs - the Latent Dirichlet Allocation, the Author-Topic and the Author-Recipient-Topic model. We extensively evaluate these models under different settings, and our results show that the Author-Recipient-Topic model extracts the most coherent topics. We also addressed the problem of topic modeling on short text by using clustering techniques. This technique helps in boosting the performance of our models. Topical alignment is used for large scale assessment of topical relevance by comparing topics to manually generated domain specific concepts. In this thesis we use this idea to evaluate topic models by measuring misalignments between topics. Our study on comparing topic models reveals interesting traits about Twitter messages, users and their interactions and establishes that joint modeling on author-recipient pairs and on the content of tweet leads to qualitatively better topic discovery. This thesis gives a new direction to the well known problem of topic discovery in microblogs. Trend prediction or topic discovery for microblogs is an extensive research area. We propose the idea of using topical alignment to detect new topics by comparing topics from the current week to those of the previous week. We measure correspondence between a set of topics from the current week and a set of topics from the previous week to quantify five types of misalignments: \textit{junk, fused, missing} and \textit{repeated}. Our analysis compares three types of topic models under different settings and demonstrates how our framework can detect new topics from topical misalignments. In particular so-called \textit{junk} topics are more likely to be new topics and the \textit{missing} topics are likely to have died or die out. To get more insights into the nature of microblogs we apply topical alignment to hashtags. Comparing topics to hashtags enables us to make interesting inferences about Twitter messages and their content. Our study revealed that although a very small proportion of Twitter messages explicitly contain hashtags, the proportion of tweets that discuss topics related to hashtags is much higher.Computer Science

Plan, Attend, Generate: Character-level Neural Machine Translation with Planning in the Decoder

We investigate the integration of a planning mechanism into an encoder-decoder architecture with an explicit alignment for character-level machine translation. We develop a model that plans ahead when it computes alignments between the source and target sequences, constructing a matrix of proposed future alignments and a commitment vector that governs whether to follow or recompute the plan. This mechanism is inspired by the strategic attentive reader and writer (STRAW) model. Our proposed model is end-to-end trainable with fully differentiable operations. We show that it outperforms a strong baseline on three character-level decoder neural machine translation on WMT'15 corpus. Our analysis demonstrates that our model can compute qualitatively intuitive alignments and achieves superior performance with fewer parameters.Comment: Accepted to Rep4NLP 2017 Workshop at ACL 2017 Conferenc

Protein alignment HW/SW optimizations

Biosequence alignment recently received an amazing support from both commodity and dedicated hardware platforms. The limitless requirements of this application motivate the search for improved implementations to boost processing time and capabilities. We propose an unprecedented hardware improvement to the classic Smith-Waterman (S-W) algorithm based on a twofold approach: i) an on-the-fly gap-open/gap-extension selection that reduces the hardware implementation complexity; ii) a pre-selection filter that uses reduced amino-acid alphabets to screen out not-significant sequences and to shorten the S-Witerations on huge reference databases.We demonstrated the improvements w.r.t. a classic approach both from the point of view of algorithm efficiency and of HW performance (FPGA and ASIC post-synthesis analysis)