Lag, lock, sync, slip: the many 'phases' of coupled flagella

This is the final version of the article. Available from the Royal Society via the DOI in this recordIn a multitude of life's processes, cilia and flagella are found indispensable. Recently, the biflagellated chlorophyte alga Chlamydomonas has become a model organism for the study of ciliary motility and synchronization. Here, we use high-speed, high-resolution imaging of single pipette-held cells to quantify the rich dynamics exhibited by their flagella. Underlying this variability in behaviour are biological dissimilarities between the two flagella—termed cis and trans, with respect to a unique eyespot. With emphasis on the wild-type, we derive limit cycles and phase parametrizations for self-sustained flagellar oscillations from digitally tracked flagellar waveforms. Characterizing interflagellar phase synchrony via a simple model of coupled oscillators with noise, we find that during the canonical swimming breaststroke the cis flagellum is consistently phase-lagged relative to, while remaining robustly phase-locked with, the trans flagellum. Transient loss of synchrony, or phase slippage, may be triggered stochastically, in which the trans flagellum transitions to a second mode of beating with attenuated beat envelope and increased frequency. Further, exploiting this alga's ability for flagellar regeneration, we mechanically induced removal of one or the other flagellum of the same cell to reveal a striking disparity between the beatings of the cis and trans flagella, in isolation. These results are evaluated in the context of the dynamic coordination of Chlamydomonas flagella.Financial support is acknowledged from the EPSRC, ERC Advanced Investigator Grant 247333, and a Senior Investigator Award from the Wellcome Trust (R.E.G.)

Aerotaxis in the closest relatives of animals

As the closest unicellular relatives of animals, choanoflagellates serve as useful model organisms for understanding the evolution of animal multicellularity. An important factor in animal evolution was the increasing ocean oxygen levels in the Precambrian, which are thought to have influenced the emergence of complex multicellular life. As a first step in addressing these conditions, we study here the response of the colony-forming choanoflagellate $\textit{Salpingoeca rosetta}$ to oxygen gradients. Using a microfluidic device that allows spatio-temporal variations in oxygen concentrations, we report the discovery that $\textit{S. rosetta}$ displays positive aerotaxis. Analysis of the spatial population distributions provides evidence for logarithmic sensing of oxygen, which enhances sensing in low oxygen neighborhoods. Analysis of search strategy models on the experimental colony trajectories finds that choanoflagellate aerotaxis is consistent with stochastic navigation, the statistics of which are captured using an effective continuous version based on classical run-and-tumble chemotaxis.Engineering and Physical Sciences Research Council, St John’s College, European Research Council (Advanced Investigator Grant ID: 247333), Wellcome Trust (Senior Investigator Award

Antiphase Synchronization in a Flagellar-Dominance Mutant of Chlamydomonas

This is the final version. Available on open access from American Physical Society via the DOI in this record. Groups of beating flagella or cilia often synchronize so that neighboring filaments have identical frequencies and phases. A prime example is provided by the unicellular biflagellate Chlamydomonas reinhardtii, which typically displays synchronous in-phase beating in a low-Reynolds number version of breaststroke swimming. We report the discovery that ptx1, a flagellar-dominance mutant of C. reinhardtii, can exhibit synchronization in precise antiphase, as in the freestyle swimming stroke. High-speed imaging shows that ptx1 flagella switch stochastically between in-phase and antiphase states, and that the latter has a distinct waveform and significantly higher frequency, both of which are strikingly similar to those found during phase slips that stochastically interrupt in-phase beating of the wild-type. Possible mechanisms underlying these observations are discussed.Spanish Ministerio de Ciencia y InnovaciónEngineering and Physical Sciences Research Council (EPSRC)Biotechnology and Biological Sciences Research Council (BBSRC)European Research CouncilWellcome Trus

Envelope: interactive software for modeling and fitting complex isotope distributions

<p>Abstract</p> <p>Background</p> <p>An important aspect of proteomic mass spectrometry involves quantifying and interpreting the isotope distributions arising from mixtures of macromolecules with different isotope labeling patterns. These patterns can be quite complex, in particular with <it>in vivo </it>metabolic labeling experiments producing fractional atomic labeling or fractional residue labeling of peptides or other macromolecules. In general, it can be difficult to distinguish the contributions of species with different labeling patterns to an experimental spectrum and difficult to calculate a theoretical isotope distribution to fit such data. There is a need for interactive and user-friendly software that can calculate and fit the entire isotope distribution of a complex mixture while comparing these calculations with experimental data and extracting the contributions from the differently labeled species.</p> <p>Results</p> <p>Envelope has been developed to be user-friendly while still being as flexible and powerful as possible. Envelope can simultaneously calculate the isotope distributions for any number of different labeling patterns for a given peptide or oligonucleotide, while automatically summing these into a single overall isotope distribution. Envelope can handle fractional or complete atom or residue-based labeling, and the contribution from each different user-defined labeling pattern is clearly illustrated in the interactive display and is individually adjustable. At present, Envelope supports labeling with ²H, ¹³C, and ¹⁵N, and supports adjustments for baseline correction, an instrument accuracy offset in the m/z domain, and peak width. Furthermore, Envelope can display experimental data superimposed on calculated isotope distributions, and calculate a least-squares goodness of fit between the two. All of this information is displayed on the screen in a single graphical user interface. Envelope supports high-quality output of experimental and calculated distributions in PNG or PDF format. Beyond simply comparing calculated distributions to experimental data, Envelope is useful for planning or designing metabolic labeling experiments, by visualizing hypothetical isotope distributions in order to evaluate the feasibility of a labeling strategy. Envelope is also useful as a teaching tool, with its real-time display capabilities providing a straightforward way to illustrate the key variable factors that contribute to an observed isotope distribution.</p> <p>Conclusion</p> <p>Envelope is a powerful tool for the interactive calculation and visualization of complex isotope distributions for comparison to experimental data. It is available under the GNU General Public License from <url>http://williamson.scripps.edu/envelope/</url>.</p

BioSunMS: a plug-in-based software for the management of patients information and the analysis of peptide profiles from mass spectrometry

<p>Abstract</p> <p>Background</p> <p>With wide applications of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), statistical comparison of serum peptide profiles and management of patients information play an important role in clinical studies, such as early diagnosis, personalized medicine and biomarker discovery. However, current available software tools mainly focused on data analysis rather than providing a flexible platform for both the management of patients information and mass spectrometry (MS) data analysis.</p> <p>Results</p> <p>Here we presented a plug-in-based software, BioSunMS, for both the management of patients information and serum peptide profiles-based statistical analysis. By integrating all functions into a user-friendly desktop application, BioSunMS provided a comprehensive solution for clinical researchers without any knowledge in programming, as well as a plug-in architecture platform with the possibility for developers to add or modify functions without need to recompile the entire application.</p> <p>Conclusion</p> <p>BioSunMS provides a plug-in-based solution for managing, analyzing, and sharing high volumes of MALDI-TOF or SELDI-TOF MS data. The software is freely distributed under GNU General Public License (GPL) and can be downloaded from <url>http://sourceforge.net/projects/biosunms/</url>.</p

Statistical quality assessment and outlier detection for liquid chromatography-mass spectrometry experiments

<p>Abstract</p> <p>Background</p> <p>Quality assessment methods, that are common place in engineering and industrial production, are not widely spread in large-scale proteomics experiments. But modern technologies such as Multi-Dimensional Liquid Chromatography coupled to Mass Spectrometry (LC-MS) produce large quantities of proteomic data. These data are prone to measurement errors and reproducibility problems such that an automatic quality assessment and control become increasingly important.</p> <p>Results</p> <p>We propose a methodology to assess the quality and reproducibility of data generated in quantitative LC-MS experiments. We introduce quality descriptors that capture different aspects of the quality and reproducibility of LC-MS data sets. Our method is based on the Mahalanobis distance and a robust Principal Component Analysis.</p> <p>Conclusion</p> <p>We evaluate our approach on several data sets of different complexities and show that we are able to precisely detect LC-MS runs of poor signal quality in large-scale studies.</p

OpenMS – An open-source software framework for mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry is an essential analytical technique for high-throughput analysis in proteomics and metabolomics. The development of new separation techniques, precise mass analyzers and experimental protocols is a very active field of research. This leads to more complex experimental setups yielding ever increasing amounts of data. Consequently, analysis of the data is currently often the bottleneck for experimental studies. Although software tools for many data analysis tasks are available today, they are often hard to combine with each other or not flexible enough to allow for rapid prototyping of a new analysis workflow.</p> <p>Results</p> <p>We present OpenMS, a software framework for rapid application development in mass spectrometry. OpenMS has been designed to be portable, easy-to-use and robust while offering a rich functionality ranging from basic data structures to sophisticated algorithms for data analysis. This has already been demonstrated in several studies.</p> <p>Conclusion</p> <p>OpenMS is available under the Lesser GNU Public License (LGPL) from the project website at <url>http://www.openms.de</url>.</p

Bioinformatics tools for cancer metabolomics

It is well known that significant metabolic change take place as cells are transformed from normal to malignant. This review focuses on the use of different bioinformatics tools in cancer metabolomics studies. The article begins by describing different metabolomics technologies and data generation techniques. Overview of the data pre-processing techniques is provided and multivariate data analysis techniques are discussed and illustrated with case studies, including principal component analysis, clustering techniques, self-organizing maps, partial least squares, and discriminant function analysis. Also included is a discussion of available software packages

Phase Synchronization of fluid-fluid interfaces as hydrodynamically coupled oscillators

Hydrodynamic interactions play a role in synchronized motions of coupled oscillators in fluids, and understanding the mechanism will facilitate development of applications in fluid mechanics. For example, synchronization phenomenon in two-phase flow will benefit the design of future microfluidic devices, allowing spatiotemporal control of microdroplet generation without additional integration of control elements. In this work, utilizing a characteristic oscillation of adjacent interfaces between two immiscible fluids in a microfluidic platform, we discover that the system can act as a coupled oscillator, notably showing spontaneous in-phase synchronization of droplet breakup. With this observation of in-phase synchronization, the coupled droplet generator exhibits a complete set of modes of coupled oscillators, including out-of-phase synchronization and nonsynchronous modes. We present a theoretical model to elucidate how a negative feedback mechanism, tied to the distance between the interfaces, induces the in-phase synchronization. We also identify the criterion for the transition from in-phase to out-of-phase oscillations