TY - JOUR AB - Background: Many cancer genomes are extensively rearranged with highly aberrant chromosomal karyotypes. Structural and copy number variations in cancer genomes can be determined via abnormal mapping of sequenced reads to the reference genome. Recently it became possible to reconcile both of these types of large-scale variations into a karyotype graph representation of the rearranged cancer genomes. Such a representation, however, does not directly describe the linear and/or circular structure of the underlying rearranged cancer chromosomes, thus limiting possible analysis of cancer genomes somatic evolutionary process as well as functional genomic changes brought by the large-scale genome rearrangements. Results: Here we address the aforementioned limitation by introducing a novel methodological framework for recovering rearranged cancer chromosomes from karyotype graphs. For a cancer karyotype graph we formulate an Eulerian Decomposition Problem (EDP) of finding a collection of linear and/or circular rearranged cancer chromosomes that are determined by the graph. We derive and prove computational complexities for several variations of the EDP. We then demonstrate that Eulerian decomposition of the cancer karyotype graphs is not always unique and present the Consistent Contig Covering Problem (CCCP) of recovering unambiguous cancer contigs from the cancer karyotype graph, and describe a novel algorithm CCR capable of solving CCCP in polynomial time. We apply CCR on a prostate cancer dataset and demonstrate that it is capable of consistently recovering large cancer contigs even when underlying cancer genomes are highly rearranged. Conclusions: CCR can recover rearranged cancer contigs from karyotype graphs thereby addressing existing limitation in inferring chromosomal structures of rearranged cancer genomes and advancing our understanding of both patient/cancer-specific as well as the overall genetic instability in cancer. AU - Aganezov, Sergey AU - Zban, Ilya AU - Aksenov, Vitalii AU - Alexeev, Nikita AU - Schatz, Michael C. ID - 7214 JF - BMC Bioinformatics TI - Recovering rearranged cancer chromosomes from karyotype graphs VL - 20 ER - TY - JOUR AB - This is a literature teaching resource review for biologically inspired microfluidics courses or exploring the diverse applications of microfluidics. The structure is around key papers and model organisms. While courses gradually change over time, a focus remains on understanding how microfluidics has developed as well as what it can and cannot do for researchers. As a primary starting point, we cover micro-fluid mechanics principles and microfabrication of devices. A variety of applications are discussed using model prokaryotic and eukaryotic organisms from the set of bacteria (Escherichia coli), trypanosomes (Trypanosoma brucei), yeast (Saccharomyces cerevisiae), slime molds (Physarum polycephalum), worms (Caenorhabditis elegans), flies (Drosophila melangoster), plants (Arabidopsis thaliana), and mouse immune cells (Mus musculus). Other engineering and biochemical methods discussed include biomimetics, organ on a chip, inkjet, droplet microfluidics, biotic games, and diagnostics. While we have not yet reached the end-all lab on a chip, microfluidics can still be used effectively for specific applications. AU - Merrin, Jack ID - 7225 IS - 4 JF - Bioengineering TI - Frontiers in microfluidics, a teaching resource review VL - 6 ER - TY - CONF AB - Traditional concurrent programming involves manipulating shared mutable state. Alternatives to this programming style are communicating sequential processes (CSP) and actor models, which share data via explicit communication. These models have been known for almost half a century, and have recently had started to gain significant traction among modern programming languages. The common abstraction for communication between several processes is the channel. Although channels are similar to producer-consumer data structures, they have different semantics and support additional operations, such as the select expression. Despite their growing popularity, most known implementations of channels use lock-based data structures and can be rather inefficient. In this paper, we present the first efficient lock-free algorithm for implementing a communication channel for CSP programming. We provide implementations and experimental results in the Kotlin and Go programming languages. Our new algorithm outperforms existing implementations on many workloads, while providing non-blocking progress guarantee. Our design can serve as an example of how to construct general communication data structures for CSP and actor models. AU - Koval, Nikita AU - Alistarh, Dan-Adrian AU - Elizarov, Roman ID - 7228 SN - 0302-9743 T2 - 25th Anniversary of Euro-Par TI - Scalable FIFO channels for programming via communicating sequential processes VL - 11725 ER - TY - CONF AB - We present LiveTraVeL (Live Transit Vehicle Labeling), a real-time system to label a stream of noisy observations of transit vehicle trajectories with the transit routes they are serving (e.g., northbound bus #5). In order to scale efficiently to large transit networks, our system first retrieves a small set of candidate routes from a geometrically indexed data structure, then applies a fine-grained scoring step to choose the best match. Given that real-time data remains unavailable for the majority of the world’s transit agencies, these inferences can help feed a real-time map of a transit system’s trips, infer transit trip delays in real time, or measure and correct noisy transit tracking data. This system can run on vehicle observations from a variety of sources that don’t attach route information to vehicle observations, such as public imagery streams or user-contributed transit vehicle sightings.We abstract away the specifics of the sensing system and demonstrate the effectiveness of our system on a "semisynthetic" dataset of all New York City buses, where we simulate sensed trajectories by starting with fully labeled vehicle trajectories reported via the GTFS-Realtime protocol, removing the transit route IDs, and perturbing locations with synthetic noise. Using just the geometric shapes of the trajectories, we demonstrate that our system converges on the correct route ID within a few minutes, even after a vehicle switches from serving one trip to the next. AU - Osang, Georg F AU - Cook, James AU - Fabrikant, Alex AU - Gruteser, Marco ID - 7216 SN - 9781538670248 T2 - 2019 IEEE Intelligent Transportation Systems Conference TI - LiveTraVeL: Real-time matching of transit vehicle trajectories to transit routes at scale ER - TY - CONF AB - Piecewise Barrier Tubes (PBT) is a new technique for flowpipe overapproximation for nonlinear systems with polynomial dynamics, which leverages a combination of barrier certificates. PBT has advantages over traditional time-step based methods in dealing with those nonlinear dynamical systems in which there is a large difference in speed between trajectories, producing an overapproximation that is time independent. However, the existing approach for PBT is not efficient due to the application of interval methods for enclosure-box computation, and it can only deal with continuous dynamical systems without uncertainty. In this paper, we extend the approach with the ability to handle both continuous and hybrid dynamical systems with uncertainty that can reside in parameters and/or noise. We also improve the efficiency of the method significantly, by avoiding the use of interval-based methods for the enclosure-box computation without loosing soundness. We have developed a C++ prototype implementing the proposed approach and we evaluate it on several benchmarks. The experiments show that our approach is more efficient and precise than other methods in the literature. AU - Kong, Hui AU - Bartocci, Ezio AU - Jiang, Yu AU - Henzinger, Thomas A ID - 7231 SN - 0302-9743 T2 - 17th International Conference on Formal Modeling and Analysis of Timed Systems TI - Piecewise robust barrier tubes for nonlinear hybrid systems with uncertainty VL - 11750 ER - TY - JOUR AB - Coupling of endoplasmic reticulum stress to dimerisation‑dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal domain (IRE1LD) that favours the latter's monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP‑induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling. AU - Amin-Wetzel, Niko Paresh AU - Neidhardt, Lisa AU - Yan, Yahui AU - Mayer, Matthias P. AU - Ron, David ID - 7340 JF - eLife TI - Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR VL - 8 ER - TY - JOUR AB - Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions. AU - Sokolowski, Thomas R AU - Paijmans, Joris AU - Bossen, Laurens AU - Miedema, Thomas AU - Wehrens, Martijn AU - Becker, Nils B. AU - Kaizu, Kazunari AU - Takahashi, Koichi AU - Dogterom, Marileen AU - ten Wolde, Pieter Rein ID - 7422 IS - 5 JF - The Journal of Chemical Physics SN - 0021-9606 TI - eGFRD in all dimensions VL - 150 ER - TY - CONF AB - Simple drawings of graphs are those in which each pair of edges share at most one point, either a common endpoint or a proper crossing. In this paper we study the problem of extending a simple drawing D(G) of a graph G by inserting a set of edges from the complement of G into D(G) such that the result is a simple drawing. In the context of rectilinear drawings, the problem is trivial. For pseudolinear drawings, the existence of such an extension follows from Levi’s enlargement lemma. In contrast, we prove that deciding if a given set of edges can be inserted into a simple drawing is NP-complete. Moreover, we show that the maximization version of the problem is APX-hard. We also present a polynomial-time algorithm for deciding whether one edge uv can be inserted into D(G) when {u,v} is a dominating set for the graph G. AU - Arroyo Guevara, Alan M AU - Derka, Martin AU - Parada, Irene ID - 7230 SN - 0302-9743 T2 - 27th International Symposium on Graph Drawing and Network Visualization TI - Extending simple drawings VL - 11904 ER - TY - CONF AB - We present Mixed-time Signal Temporal Logic (STL−MX), a specification formalism which extends STL by capturing the discrete/ continuous time duality found in many cyber-physical systems (CPS), as well as mixed-signal electronic designs. In STL−MX, properties of components with continuous dynamics are expressed in STL, while specifications of components with discrete dynamics are written in LTL. To combine the two layers, we evaluate formulas on two traces, discrete- and continuous-time, and introduce two interface operators that map signals, properties and their satisfaction signals across the two time domains. We show that STL-mx has the expressive power of STL supplemented with an implicit T-periodic clock signal. We develop and implement an algorithm for monitoring STL-mx formulas and illustrate the approach using a mixed-signal example. AU - Ferrere, Thomas AU - Maler, Oded AU - Nickovic, Dejan ID - 7232 SN - 0302-9743 T2 - 17th International Conference on Formal Modeling and Analysis of Timed Systems TI - Mixed-time signal temporal logic VL - 11750 ER - TY - JOUR AB - β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic. AU - Sahgal, Pranshu AU - Alanko, Jonna H AU - Icha, Jaroslav AU - Paatero, Ilkka AU - Hamidi, Hellyeh AU - Arjonen, Antti AU - Pietilä, Mika AU - Rokka, Anne AU - Ivaska, Johanna ID - 7420 IS - 11 JF - Journal of Cell Science SN - 0021-9533 TI - GGA2 and RAB13 promote activity-dependent β1-integrin recycling VL - 132 ER -