@article{831, abstract = {In Arabidopsis, lateral roots originate from pericycle cells deep within the primary root. New lateral root primordia (LRP) have to emerge through several overlaying tissues. Here, we report that auxin produced in new LRP is transported towards the outer tissues where it triggers cell separation by inducing both the auxin influx carrier LAX3 and cell-wall enzymes. LAX3 is expressed in just two cell files overlaying new LRP. To understand how this striking pattern of LAX3 expression is regulated, we developed a mathematical model that captures the network regulating its expression and auxin transport within realistic three-dimensional cell and tissue geometries. Our model revealed that, for the LAX3 spatial expression to be robust to natural variations in root tissue geometry, an efflux carrier is required--later identified to be PIN3. To prevent LAX3 from being transiently expressed in multiple cell files, PIN3 and LAX3 must be induced consecutively, which we later demonstrated to be the case. Our study exemplifies how mathematical models can be used to direct experiments to elucidate complex developmental processes.}, author = {Péret, Benjamin and Middleton, Alistair M and French, Andrew P and Larrieu, Antoine and Bishopp, Anthony and Njo, Maria and Wells, Darren M and Porco, Silvana and Mellor, Nathan and Band, Leah R and Casimiro, Ilda and Kleine-Vehn, Jürgen and Vanneste, Steffen and Sairanen, Ilkka and Mallet, Romain and Sandberg, Göran and Ljung, Karin and Beeckman, Tom and Eva Benková and Jirí Friml and Kramer, Eric and King, John R and De Smet, Ive and Pridmore, Tony and Owen, Markus and Bennett, Malcolm J}, journal = {Molecular Systems Biology}, publisher = {Nature Publishing Group}, title = {{Sequential induction of auxin efflux and influx carriers regulates lateral root emergence}}, doi = {10.1038/msb.2013.43}, volume = {9}, year = {2013}, } @article{8461, abstract = {Solid-state NMR provides insight into protein motion over time scales ranging from picoseconds to seconds. While in solution state the methodology to measure protein dynamics is well established, there is currently no such consensus protocol for measuring dynamics in solids. In this article, we perform a detailed investigation of measurement protocols for fast motions, i.e. motions ranging from picoseconds to a few microseconds, which is the range covered by dipolar coupling and relaxation experiments. We perform a detailed theoretical investigation how dipolar couplings and relaxation data can provide information about amplitudes and time scales of local motion. We show that the measurement of dipolar couplings is crucial for obtaining accurate motional parameters, while systematic errors are found when only relaxation data are used. Based on this realization, we investigate how the REDOR experiment can provide such data in a very accurate manner. We identify that with accurate rf calibration, and explicit consideration of rf field inhomogeneities, one can obtain highly accurate absolute order parameters. We then perform joint model-free analyses of 6 relaxation data sets and dipolar couplings, based on previously existing, as well as new data sets on microcrystalline ubiquitin. We show that nanosecond motion can be detected primarily in loop regions, and compare solid-state data to solution-state relaxation and RDC analyses. The protocols investigated here will serve as a useful basis towards the establishment of a routine protocol for the characterization of ps–μs motions in proteins by solid-state NMR.}, author = {Haller, Jens D. and Schanda, Paul}, issn = {0925-2738}, journal = {Journal of Biomolecular NMR}, keywords = {Spectroscopy, Biochemistry}, number = {3}, pages = {263--280}, publisher = {Springer Nature}, title = {{Amplitudes and time scales of picosecond-to-microsecond motion in proteins studied by solid-state NMR: a critical evaluation of experimental approaches and application to crystalline ubiquitin}}, doi = {10.1007/s10858-013-9787-x}, volume = {57}, year = {2013}, } @article{8462, abstract = {The transition of proteins from their soluble functional state to amyloid fibrils and aggregates is associated with the onset of several human diseases. Protein aggregation often requires some structural reshaping and the subsequent formation of intermolecular contacts. Therefore, the study of the conformation of excited protein states and their ability to form oligomers is of primary importance for understanding the molecular basis of amyloid fibril formation. Here, we investigated the oligomerization processes that occur along the folding of the amyloidogenic human protein β2-microglobulin. The combination of real-time two-dimensional NMR data with real-time small-angle X-ray scattering measurements allowed us to derive thermodynamic and kinetic information on protein oligomerization of different conformational states populated along the folding pathways. In particular, we could demonstrate that a long-lived folding intermediate (I-state) has a higher propensity to oligomerize compared to the native state. Our data agree well with a simple five-state kinetic model that involves only monomeric and dimeric species. The dimers have an elongated shape with the dimerization interface located at the apical side of β2-microglobulin close to Pro32, the residue that has a trans conformation in the I-state and a cis conformation in the native (N) state. Our experimental data suggest that partial unfolding in the apical half of the protein close to Pro32 leads to an excited state conformation with enhanced propensity for oligomerization. This excited state becomes more populated in the transient I-state due to the destabilization of the native conformation by the trans-Pro32 configuration.}, author = {Rennella, E. and Cutuil, T. and Schanda, Paul and Ayala, I. and Gabel, F. and Forge, V. and Corazza, A. and Esposito, G. and Brutscher, B.}, issn = {0022-2836}, journal = {Journal of Molecular Biology}, keywords = {Molecular Biology}, number = {15}, pages = {2722--2736}, publisher = {Elsevier}, title = {{Oligomeric states along the folding pathways of β2-microglobulin: Kinetics, thermodynamics, and structure}}, doi = {10.1016/j.jmb.2013.04.028}, volume = {425}, year = {2013}, } @article{894, abstract = {Background: Genetic variation at the melanocortin-1 receptor (MC1R) gene is correlated with melanin color variation in many birds. Feral pigeons (Columba livia) show two major melanin-based colorations: a red coloration due to pheomelanic pigment and a black coloration due to eumelanic pigment. Furthermore, within each color type, feral pigeons display continuous variation in the amount of melanin pigment present in the feathers, with individuals varying from pure white to a full dark melanic color. Coloration is highly heritable and it has been suggested that it is under natural or sexual selection, or both. Our objective was to investigate whether MC1R allelic variants are associated with plumage color in feral pigeons. Findings. We sequenced 888 bp of the coding sequence of MC1R among pigeons varying both in the type, eumelanin or pheomelanin, and the amount of melanin in their feathers. We detected 10 non-synonymous substitutions and 2 synonymous substitution but none of them were associated with a plumage type. It remains possible that non-synonymous substitutions that influence coloration are present in the short MC1R fragment that we did not sequence but this seems unlikely because we analyzed the entire functionally important region of the gene. Conclusions: Our results show that color differences among feral pigeons are probably not attributable to amino acid variation at the MC1R locus. Therefore, variation in regulatory regions of MC1R or variation in other genes may be responsible for the color polymorphism of feral pigeons.}, author = {Derelle, Romain and Kondrashov, Fyodor and Arkhipov, Vladimir and Corbel, Hélène and Frantz, Adrien and Gasparini, Julien and Jacquin, Lisa and Jacob, Gwenaël and Thibault, Sophie and Baudry, Emmanuelle}, journal = {BMC Research Notes}, number = {1}, publisher = {BioMed Central}, title = {{Color differences among feral pigeons (Columba livia) are not attributable to sequence variation in the coding region of the melanocortin-1 receptor gene MC1R}}, doi = {10.1186/1756-0500-6-310}, volume = {6}, year = {2013}, } @article{899, abstract = {Understanding fitness landscapes, a conceptual depiction of the genotype-to-phenotype relationship, is crucial to many areas of biology. Two aspects of fitness landscapes are the focus of contemporary studies of molecular evolution. First, the local shape of the fitness landscape defined by the contribution of individual alleles to fitness that is independent of all genetic interactions. Second, the global, multidimensional fitness landscape shape determined by how interactions between alleles at different loci change each other’s fitness impact, or epistasis. In explaining the high amino-acid usage (u), we focused on the global shape of the fitness landscape, ignoring the perturbations at individual sites.}, author = {Breen, Michael S and Kemena, Carsten and Vlasov, Peter K and Notredame, Cédric and Fyodor Kondrashov}, journal = {Nature}, number = {7451}, pages = {E2 -- E3}, publisher = {Nature Publishing Group}, title = {{Breen et al. reply}}, doi = {10.1038/nature12220}, volume = {497}, year = {2013}, } @article{1726, abstract = {The development of a functional tissue requires coordination of the amplification of progenitors and their differentiation into specific cell types. The molecular basis for this coordination during myotome ontogeny is not well understood. Dermomytome progenitors that colonize the myotome first acquire myocyte identity and subsequently proliferate as Pax7-expressing progenitors before undergoing terminal differentiation. We show that the dynamics of sonic hedgehog (Shh) signaling is crucial for this transition in both avian and mouse embryos. Initially, Shh ligand emanating from notochord/floor plate reaches the dermomyotome, where it both maintains the proliferation of dermomyotome cells and promotes myogenic differentiation of progenitors that colonized the myotome. Interfering with Shh signaling at this stage produces small myotomes and accumulation of Pax7-expressing progenitors. An in vivo reporter of Shh activity combined with mouse genetics revealed the existence of both activator and repressor Shh activities operating on distinct subsets of cells during the epaxial myotomal maturation. In contrast to observations in mice, in avians Shh promotes the differentiation of both epaxial and hypaxial myotome domains. Subsequently, myogenic progenitors become refractory to Shh; this is likely to occur at the level of, or upstream of, smoothened signaling. The end of responsiveness to Shh coincides with, and is thus likely to enable, the transition into the growth phase of the myotome.}, author = {Kahane, Nitza and Ribes, Vanessa and Anna Kicheva and Briscoe, James and Kalcheim, Chaya}, journal = {Development}, number = {8}, pages = {1740 -- 1750}, publisher = {Company of Biologists}, title = {{The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling}}, doi = {10.1242/dev.092726}, volume = {140}, year = {2013}, } @article{1727, abstract = {Cells at different positions in a developing tissue receive different concentrations of signaling molecules, called morphogens, and this influences their cell fate. Morphogen concentration gradients have been proposed to control patterning as well as growth in many developing tissues. Some outstanding questions about tissue patterning by morphogen gradients are the following: What are the mechanisms that regulate gradient formation and shape? Is the positional information encoded in the gradient sufficiently precise to determine the positions of target gene domain boundaries? What are the temporal dynamics of gradients and how do they relate to patterning and growth? These questions are inherently quantitative in nature and addressing them requires measuring morphogen concentrations in cells, levels of downstream signaling activity, and kinetics of morphogen transport. Here we first present methods for quantifying morphogen gradient shape in which the measurements can be calibrated to reflect actual morphogen concentrations. We then discuss using fluorescence recovery after photobleaching to study the kinetics of morphogen transport at the tissue level. Finally, we present particle tracking as a method to study morphogen intracellular trafficking.}, author = {Anna Kicheva and Holtzer, Laurent and Wartlick, Ortrud and Schmidt, Thomas S and González-Gaitán, Marcos A}, journal = {Cold Spring Harbor Protocols}, number = {5}, pages = {387 -- 403}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Quantitative imaging of morphogen gradients in drosophila imaginal discs}}, doi = {10.1101/pdb.top074237}, volume = {8}, year = {2013}, } @article{1759, abstract = {We report an electric-field-induced giant modulation of the hole g factor in SiGe nanocrystals. The observed effect is ascribed to a so-far overlooked contribution to the g factor that stems from the mixing between heavy- and light-hole wave functions. We show that the relative displacement between the confined heavy- and light-hole states, occurring upon application of the electric field, alters their mixing strength leading to a strong nonmonotonic modulation of the g factor.}, author = {Ares, Natalia and Golovach, Vitaly N and Georgios Katsaros and Stoffel, Mathieu and Fournel, Frank and Glazman, Leonid I and Schmidt, Oliver G and De Franceschi, Silvano}, journal = {Physical Review Letters}, number = {4}, publisher = {American Physical Society}, title = {{Nature of tunable hole g factors in quantum dots}}, doi = {10.1103/PhysRevLett.110.046602}, volume = {110}, year = {2013}, } @article{1760, abstract = {We report on hole g-factor measurements in three terminal SiGe self-assembled quantum dot devices with a top gate electrode positioned very close to the nanostructure. Measurements of both the perpendicular as well as the parallel g-factor reveal significant changes for a small modulation of the top gate voltage. From the observed modulations, we estimate that, for realistic experimental conditions, hole spins can be electrically manipulated with Rabi frequencies in the order of 100 MHz. This work emphasises the potential of hole-based nano-devices for efficient spin manipulation by means of the g-tensor modulation technique.}, author = {Ares, Natalia and Georgios Katsaros and Golovach, Vitaly N and Zhang, Jianjun and Prager, Aaron A and Glazman, Leonid I and Schmidt, Oliver G and De Franceschi, Silvano}, journal = {Applied Physics Letters}, number = {26}, publisher = {American Institute of Physics}, title = {{SiGe quantum dots for fast hole spin Rabi oscillations}}, doi = {10.1063/1.4858959}, volume = {103}, year = {2013}, } @article{1785, abstract = {The geometric aspects of quantum mechanics are emphasized most prominently by the concept of geometric phases, which are acquired whenever a quantum system evolves along a path in Hilbert space, that is, the space of quantum states of the system. The geometric phase is determined only by the shape of this path and is, in its simplest form, a real number. However, if the system has degenerate energy levels, then matrix-valued geometric state transformations, known as non-Abelian holonomies-the effect of which depends on the order of two consecutive paths-can be obtained. They are important, for example, for the creation of synthetic gauge fields in cold atomic gases or the description of non-Abelian anyon statistics. Moreover, there are proposals to exploit non-Abelian holonomic gates for the purposes of noise-resilient quantum computation. In contrast to Abelian geometric operations, non-Abelian ones have been observed only in nuclear quadrupole resonance experiments with a large number of spins, and without full characterization of the geometric process and its non-commutative nature. Here we realize non-Abelian non-adiabatic holonomic quantum operations on a single, superconducting, artificial three-level atom by applying a well-controlled, two-tone microwave drive. Using quantum process tomography, we determine fidelities of the resulting non-commuting gates that exceed 95 per cent. We show that two different quantum gates, originating from two distinct paths in Hilbert space, yield non-equivalent transformations when applied in different orders. This provides evidence for the non-Abelian character of the implemented holonomic quantum operations. In combination with a non-trivial two-quantum-bit gate, our method suggests a way to universal holonomic quantum computing.}, author = {Abdumalikov, Abdufarrukh A and Johannes Fink and Juliusson, K and Pechal, M and Berger, Stefan T and Wallraff, Andreas and Filipp, Stefan}, journal = {Nature}, number = {7446}, pages = {482 -- 485}, publisher = {Nature Publishing Group}, title = {{Experimental realization of non-Abelian non-adiabatic geometric gates}}, doi = {10.1038/nature12010}, volume = {496}, year = {2013}, } @article{1786, abstract = {We report the experimental observation and a theoretical explanation of collective suppression of linewidths for multiple superconducting qubits coupled to a good cavity. This demonstrates how strong qubit-cavity coupling can significantly modify the dephasing and dissipation processes that might be expected for individual qubits, and can potentially improve coherence times in many-body circuit QED.}, author = {Nissen, Felix and Johannes Fink and Mlynek, Jonas A and Wallraff, Andreas and Keeling, Jonathan M}, journal = {Physical Review Letters}, number = {20}, publisher = {American Physical Society}, title = {{Collective suppression of linewidths in circuit QED}}, doi = {10.1103/PhysRevLett.110.203602}, volume = {110}, year = {2013}, } @article{1787, abstract = {When two indistinguishable single photons impinge at the two inputs of a beam splitter they coalesce into a pair of photons appearing in either one of its two outputs. This effect is due to the bosonic nature of photons and was first experimentally observed by Hong, Ou and Mandel. Here, we present the observation of the Hong-Ou-Mandel effect with two independent single-photon sources in the microwave frequency domain. We probe the indistinguishability of single photons, created with a controllable delay, in time-resolved second-order cross- and auto-correlation function measurements. Using quadrature amplitude detection we are able to resolve different photon numbers and detect coherence in and between the output arms. This scheme allows us to fully characterize the two-mode entanglement of the spatially separated beam-splitter output modes. Our experiments constitute a first step towards using two-photon interference at microwave frequencies for quantum communication and information processing.}, author = {Lang, C and Eichler, Christopher and Steffen, L. Kraig and Johannes Fink and Woolley, Matthew J and Blais, Alexandre and Wallraff, Andreas}, journal = {Nature Physics}, number = {6}, pages = {345 -- 348}, publisher = {Nature Publishing Group}, title = {{Correlations, indistinguishability and entanglement in Hong-Ou-Mandel experiments at microwave frequencies}}, doi = {10.1038/nphys2612}, volume = {9}, year = {2013}, } @article{1790, abstract = {In the September 12, 2013 issue of Nature, the Epi4K Consortium (. Allen etal., 2013) reported sequencing 264patient trios with epileptic encephalopathies. The Consortium focused on genes exceptionally intolerant to sequence variations and found substantial interconnections with autism and intellectual disability gene networks.}, author = {Gaia Novarino and Baek, SeungTae and Gleeson, Joseph G}, journal = {Neuron}, number = {1}, pages = {9 -- 11}, publisher = {Elsevier}, title = {{The sacred disease: The puzzling genetics of epileptic disorders}}, doi = {10.1016/j.neuron.2013.09.019}, volume = {80}, year = {2013}, } @article{1977, abstract = {Complex I (NADH:ubiquinone oxidoreductase) is central to cellular energy production, being the first and largest enzyme of the respiratory chain in mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the inner mitochondrial membrane and is involved in a wide range of human neurodegenerative disorders. Mammalian complex I is composed of 44 different subunits, whereas the 'minimal' bacterial version contains 14 highly conserved 'core' subunits. The L-shaped assembly consists of hydrophilic and membrane domains. We have determined all known atomic structures of complex I, starting from the hydrophilic domain of Thermus thermophilus enzyme (eight subunits, nine Fe-S clusters), followed by the membrane domains of the Escherichia coli (six subunits, 55 transmembrane helices) and T. thermophilus (seven subunits, 64 transmembrane helices) enzymes, and finally culminating in a recent crystal structure of the entire intact complex I from T. thermophilus (536 kDa, 16 subunits, nine Fe-S clusters, 64 transmembrane helices). The structure suggests an unusual and unique coupling mechanism via longrange conformational changes. Determination of the structure of the entire complex was possible only through this step-by-step approach, building on from smaller subcomplexes towards the entire assembly. Large membrane proteins are notoriously difficult to crystallize, and so various non-standard and sometimes counterintuitive approaches were employed in order to achieve crystal diffraction to high resolution and solve the structures. These steps, as well as the implications from the final structure, are discussed in the present review.}, author = {Leonid Sazanov and Baradaran, Rozbeh and Efremov, Rouslan G and Berrisford, John M and Minhas, Gurdeep S}, journal = {Biochemical Society Transactions}, number = {5}, pages = {1265 -- 1271}, publisher = {Portland Press}, title = {{A long road towards the structure of respiratory complex I, a giant molecular proton pump}}, doi = {10.1042/BST20130193}, volume = {41}, year = {2013}, } @article{1978, abstract = {Complex I is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of NADH:ubiquinone electron transfer to proton translocation. It is also implicated in many common human neurodegenerative diseases. Here, we report the first crystal structure of the entire, intact complex I (from Thermus thermophilus) at 3.3 Å resolution. The structure of the 536-kDa complex comprises 16 different subunits, with a total of 64 transmembrane helices and 9 iron-sulphur clusters. The core fold of subunit Nqo8 (ND1 in humans) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, which completes the fourth proton-translocation pathway (present in addition to the channels in three antiporter-like subunits). The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near iron-sulphur cluster N2. Notably, the chamber is linked to the fourth channel by a 'funnel' of charged residues. The link continues over the entire membrane domain as a flexible central axis of charged and polar residues, and probably has a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone-reaction chamber enables the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle.}, author = {Baradaran, Rozbeh and Berrisford, John M and Minhas, Gurdeep S and Leonid Sazanov}, journal = {Nature}, number = {7438}, pages = {443 -- 448}, publisher = {Nature Publishing Group}, title = {{Crystal structure of the entire respiratory complex i}}, doi = {10.1038/nature11871}, volume = {494}, year = {2013}, } @article{1988, abstract = {The rod-shaped bacterium Escherichia coli selects the cell center as site of division with the help of the proteins MinC, MinD, and MinE. This protein system collectively oscillates between the two cell poles by alternately binding to the membrane in one of the two cell halves. This dynamic behavior, which emerges from the interaction of the ATPase MinD and its activator MinE on the cell membrane, has become a paradigm for protein self-organization. Recently, it has been found that not only the binding of MinD to the membrane, but also interactions of MinE with the membrane contribute to Min-protein self-organization. Here, we show that by accounting for this finding in a computational model, we can comprehensively describe all observed Min-protein patterns in vivo and in vitro. Furthermore, by varying the system's geometry, our computations predict patterns that have not yet been reported. We confirm these predictions experimentally.}, author = {Bonny, Mike and Fischer-Friedrich, Elisabeth and Martin Loose and Schwille, Petra and Kruse, Karsten}, journal = {PLoS Computational Biology}, number = {12}, publisher = {Public Library of Science}, title = {{Membrane binding of MinE allows for a comprehensive description of Min-protein pattern formation}}, doi = {10.1371/journal.pcbi.1003347}, volume = {9}, year = {2013}, } @article{1991, abstract = {Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes, heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations. Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination or its targeting by a chromosome-specific regulatory mechanism. We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur.}, author = {Beatriz Vicoso and Bachtrog, Doris}, journal = {Nature}, number = {7458}, pages = {332 -- 335}, publisher = {Nature Publishing Group}, title = {{Reversal of an ancient sex chromosome to an autosome in Drosophila}}, doi = {10.1038/nature12235}, volume = {499}, year = {2013}, } @inproceedings{2000, abstract = {In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.}, author = {Reiter, Johannes and Božić, Ivana and Chatterjee, Krishnendu and Nowak, Martin}, booktitle = {Proceedings of 25th Int. Conf. on Computer Aided Verification}, location = {St. Petersburg, Russia}, pages = {101 -- 106}, publisher = {Springer}, title = {{TTP: Tool for tumor progression}}, doi = {10.1007/978-3-642-39799-8_6}, volume = {8044}, year = {2013}, } @article{2009, abstract = {Traditional statistical methods for confidentiality protection of statistical databases do not scale well to deal with GWAS databases especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach which provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual’s privacy. We present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. We compare these approaches on simulated data and on a GWAS study of canine hair length involving 685 dogs. We also propose a privacy-preserving method for finding genome-wide associations based on a differentially-private approach to penalized logistic regression.}, author = {Uhler, Caroline and Slavkovic, Aleksandra and Fienberg, Stephen}, journal = {Journal of Privacy and Confidentiality }, number = {1}, pages = {137 -- 166}, publisher = {Carnegie Mellon University}, title = {{Privacy-preserving data sharing for genome-wide association studies}}, doi = {10.29012/jpc.v5i1.629}, volume = {5}, year = {2013}, } @article{2010, abstract = {Many algorithms for inferring causality rely heavily on the faithfulness assumption. The main justification for imposing this assumption is that the set of unfaithful distributions has Lebesgue measure zero, since it can be seen as a collection of hypersurfaces in a hypercube. However, due to sampling error the faithfulness condition alone is not sufficient for statistical estimation, and strong-faithfulness has been proposed and assumed to achieve uniform or high-dimensional consistency. In contrast to the plain faithfulness assumption, the set of distributions that is not strong-faithful has nonzero Lebesgue measure and in fact, can be surprisingly large as we show in this paper. We study the strong-faithfulness condition from a geometric and combinatorial point of view and give upper and lower bounds on the Lebesgue measure of strong-faithful distributions for various classes of directed acyclic graphs. Our results imply fundamental limitations for the PC-algorithm and potentially also for other algorithms based on partial correlation testing in the Gaussian case.}, author = {Uhler, Caroline and Raskutti, Garvesh and Bühlmann, Peter and Yu, Bin}, journal = {The Annals of Statistics}, number = {2}, pages = {436 -- 463}, publisher = {Institute of Mathematical Statistics}, title = {{Geometry of the faithfulness assumption in causal inference}}, doi = {10.1214/12-AOS1080}, volume = {41}, year = {2013}, }