Parallel methods for short read assembly

This work is on the parallel de novo assembly of genomic sequences from short sequence reads. With short reads eliminating the reliability of read overlaps in predicting genomic co-location, a revival of graph-based methods has underpinned the development of short-read assemblers. While these methods predate short read technology, their reach has not extended significantly beyond bacterial genomes due to the memory resources required in their use. These memory limitations are exacerbated by the high coverage needed to compensate for shorter read lengths. As a result, prior to our work, short-read de novo assembly had been demonstrated on relatively small genome sizes with a few million bases. In our work, we advance the field of short sequence assembly in a number of ways. First, we extend models and ideas proposed and tested with small genomes on serial machines to large-scale distributed memory parallel machines. Second, we present ideas for assembly that are especially suited to the reconstruction of very large genomes on these machines. Additionally, we present the first assembler that specifically takes advantage a variable number of fragment sizes or insert lengths concurrently when making assembly decisions, while still working well for data with one insertion length

Time window temporal logic

This paper introduces time window temporal logic (TWTL), a rich expressive language for describing various time bounded specifications. In particular, the syntax and semantics of TWTL enable the compact representation of serial tasks, which are prevalent in various applications including robotics, sensor systems, and manufacturing systems. This paper also discusses the relaxation of TWTL formulae with respect to the deadlines of the tasks. Efficient automata-based frameworks are presented to solve synthesis, verification and learning problems. The key ingredient to the presented solution is an algorithm to translate a TWTL formula to an annotated finite state automaton that encodes all possible temporal relaxations of the given formula. Some case studies are presented to illustrate the expressivity of the logic and the proposed algorithms

Time Window Temporal Logic

This paper introduces time window temporal logic (TWTL), a rich expressivity language for describing various time bounded specifications. In particular, the syntax and semantics of TWTL enable the compact representation of serial tasks, which are typically seen in robotics and control applications. This paper also discusses the relaxation of TWTL formulae with respect to deadlines of tasks. Efficient automata-based frameworks to solve synthesis, verification and learning problems are also presented. The key ingredient to the presented solution is an algorithm to translate a TWTL formula to an annotated finite state automaton that encodes all possible temporal relaxations of the specification. Case studies illustrating the expressivity of the logic and the proposed algorithms are included

Motion planning and control: a formal methods approach

Control of complex systems satisfying rich temporal specification has become an increasingly important research area in fields such as robotics, control, automotive, and manufacturing. Popular specification languages include temporal logics, such as Linear Temporal Logic (LTL) and Computational Tree Logic (CTL), which extend propositional logic to capture the temporal sequencing of system properties. The focus of this dissertation is on the control of high-dimensional systems and on timed specifications that impose explicit time bounds on the satisfaction of tasks. This work proposes and evaluates methods and algorithms for synthesizing provably correct control policies that deal with the scalability problems. Ideas and tools from formal verification, graph theory, and incremental computing are used to synthesize satisfying control strategies. Finite abstractions of the systems are generated, and then composed with automata encoding the specifications. The first part of this dissertation introduces a sampling-based motion planning algorithm that combines long-term temporal logic goals with short-term reactive requirements. The specification has two parts: (1) a global specification given as an LTL formula over a set of static service requests that occur at the regions of a known environment, and (2) a local specification that requires servicing a set of dynamic requests that can be sensed locally during the execution. The proposed computational framework consists of two main ingredients: (a) an off-line sampling-based algorithm for the construction of a global transition system that contains a path satisfying the LTL formula, and (b) an on-line sampling-based algorithm to generate paths that service the local requests, while making sure that the satisfaction of the global specification is not affected. The second part of the dissertation focuses on stochastic systems with temporal and uncertainty constraints. A specification language called Gaussian Distribution Temporal Logic is introduced as an extension of Boolean logic that incorporates temporal evolution and noise mitigation directly into the task specifications. A sampling-based algorithm to synthesize control policies is presented that generates a transition system in the belief space and uses local feedback controllers to break the curse of history associated with belief space planning. Switching control policies are then computed using a product Markov Decision Process between the transition system and the Rabin automaton encoding the specification.The approach is evaluated in experiments using a camera network and ground robot. The third part of this dissertation focuses on control of multi-vehicle systems with timed specifications and charging constraints. A rich expressivity language called Time Window Temporal Logic (TWTL) that describes time bounded specifications is introduced. The temporal relaxation of TWTL formulae with respect to the deadlines of tasks is also discussed. The key ingredient of the solution is an algorithm to translate a TWTL formula to an annotated finite state automaton that encodes all possible temporal relaxations of the given formula. The annotated automata are composed with transition systems encoding the motion of all vehicles, and with charging models to produce control strategies for all vehicles such that the overall system satisfies the mission specification. The methods are evaluated in simulation and experimental trials with quadrotors and charging stations

Quantification and Simulation of Liquid Chromatography-Mass Spectrometry Data

Computational mass spectrometry is a fast evolving field that has attracted increased attention over the last couple of years. The performance of software solutions determines the success of analysis to a great extent. New algorithms are required to reflect new experimental procedures and deal with new instrument generations. One essential component of algorithm development is the validation (as well as comparison) of software on a broad range of data sets. This requires a gold standard (or so-called ground truth), which is usually obtained by manual annotation of a real data set. Comprehensive manually annotated public data sets for mass spectrometry data are labor-intensive to produce and their quality strongly depends on the skill of the human expert. Some parts of the data may even be impossible to annotate due to high levels of noise or other ambiguities. Furthermore, manually annotated data is usually not available for all steps in a typical computational analysis pipeline. We thus developed the most comprehensive simulation software to date, which allows to generate multiple levels of ground truth and features a plethora of settings to reflect experimental conditions and instrument settings. The simulator is used to generate several distinct types of data. The data are subsequently employed to evaluate existing algorithms. Additionally, we employ simulation to determine the influence of instrument attributes and sample complexity on the ability of algorithms to recover information. The results give valuable hints on how to optimize experimental setups. Furthermore, this thesis introduces two quantitative approaches, namely a decharging algorithm based on integer linear programming and a new workflow for identification of differentially expressed proteins for a large in vitro study on toxic compounds. Decharging infers the uncharged mass of a peptide (or protein) by clustering all its charge variants. The latter occur frequently under certain experimental conditions. We employ simulation to show that decharging is robust against missing values even for high complexity data and that the algorithm outperforms other solutions in terms of mass accuracy and run time on real data. The last part of this thesis deals with a new state-of-the-art workflow for protein quantification based on isobaric tags for relative and absolute quantitation (iTRAQ). We devise a new approach to isotope correction, propose an experimental design, introduce new metrics of iTRAQ data quality, and confirm putative properties of iTRAQ data using a novel approach. All tools developed as part of this thesis are implemented in OpenMS, a C++ library for computational mass spectrometry

Learning Formal Specifications from Membership and Preference Queries

Active learning is a well-studied approach to learning formal specifications, such as automata. In this work, we extend active specification learning by proposing a novel framework that strategically requests a combination of membership labels and pair-wise preferences, a popular alternative to membership labels. The combination of pair-wise preferences and membership labels allows for a more flexible approach to active specification learning, which previously relied on membership labels only. We instantiate our framework in two different domains, demonstrating the generality of our approach. Our results suggest that learning from both modalities allows us to robustly and conveniently identify specifications via membership and preferences.Comment: 6 pages, Presented at ICML 2023 Workshop on The Many Facets of Preference-Based Learnin