TY - JOUR AB - Multiple sequence alignments (MSAs) are used for structural1,2 and evolutionary predictions1,2, but the complexity of aligning large datasets requires the use of approximate solutions3, including the progressive algorithm4. Progressive MSA methods start by aligning the most similar sequences and subsequently incorporate the remaining sequences, from leaf-to-root, based on a guide-tree. Their accuracy declines substantially as the number of sequences is scaled up5. We introduce a regressive algorithm that enables MSA of up to 1.4 million sequences on a standard workstation and substantially improves accuracy on datasets larger than 10,000 sequences. Our regressive algorithm works the other way around to the progressive algorithm and begins by aligning the most dissimilar sequences. It uses an efficient divide-and-conquer strategy to run third-party alignment methods in linear time, regardless of their original complexity. Our approach will enable analyses of extremely large genomic datasets such as the recently announced Earth BioGenome Project, which comprises 1.5 million eukaryotic genomes6. AU - Garriga, Edgar AU - Di Tommaso, Paolo AU - Magis, Cedrik AU - Erb, Ionas AU - Mansouri, Leila AU - Baltzis, Athanasios AU - Laayouni, Hafid AU - Kondrashov, Fyodor AU - Floden, Evan AU - Notredame, Cedric ID - 7181 IS - 12 JF - Nature Biotechnology SN - 10870156 TI - Large multiple sequence alignments with a root-to-leaf regressive method VL - 37 ER - TY - JOUR AB - The cerebral cortex contains multiple areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modelling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas. AU - Llorca, Alfredo AU - Ciceri, Gabriele AU - Beattie, Robert J AU - Wong, Fong Kuan AU - Diana, Giovanni AU - Serafeimidou-Pouliou, Eleni AU - Fernández-Otero, Marian AU - Streicher, Carmen AU - Arnold, Sebastian J. AU - Meyer, Martin AU - Hippenmeyer, Simon AU - Maravall, Miguel AU - Marín, Oscar ID - 7202 JF - eLife TI - A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture VL - 8 ER - TY - JOUR AB - Glutamate is the major excitatory neurotransmitter in the CNS binding to a variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8) can act excitatory or inhibitory, depending on associated signal cascades. Expression and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3, and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants. Using receptor-specific antibodies in cochlear wholemounts, we found expression of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution and confocal microscopy in combination with 3-dimensional reconstructions indicated a postsynaptic localization of mGluR2 that overlaps with postsynaptic density protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast, mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary, we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament for new therapeutical strategies that could protect the cochlea against noxious stimuli and excitotoxicity. AU - Klotz, Lisa AU - Wendler, Olaf AU - Frischknecht, Renato AU - Shigemoto, Ryuichi AU - Schulze, Holger AU - Enz, Ralf ID - 7179 IS - 12 JF - FASEB Journal TI - Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses VL - 33 ER - TY - CONF AB - Applying machine learning techniques to the quickly growing data in science and industry requires highly-scalable algorithms. Large datasets are most commonly processed "data parallel" distributed across many nodes. Each node's contribution to the overall gradient is summed using a global allreduce. This allreduce is the single communication and thus scalability bottleneck for most machine learning workloads. We observe that frequently, many gradient values are (close to) zero, leading to sparse of sparsifyable communications. To exploit this insight, we analyze, design, and implement a set of communication-efficient protocols for sparse input data, in conjunction with efficient machine learning algorithms which can leverage these primitives. Our communication protocols generalize standard collective operations, by allowing processes to contribute arbitrary sparse input data vectors. Our generic communication library, SparCML1, extends MPI to support additional features, such as non-blocking (asynchronous) operations and low-precision data representations. As such, SparCML and its techniques will form the basis of future highly-scalable machine learning frameworks. AU - Renggli, Cedric AU - Ashkboos, Saleh AU - Aghagolzadeh, Mehdi AU - Alistarh, Dan-Adrian AU - Hoefler, Torsten ID - 7201 SN - 21674329 T2 - International Conference for High Performance Computing, Networking, Storage and Analysis, SC TI - SparCML: High-performance sparse communication for machine learning ER - TY - GEN AB - Genetic incompatibilities contribute to reproductive isolation between many diverging populations, but it is still unclear to what extent they play a role if divergence happens with gene flow. In contact zones between the "Crab" and "Wave" ecotypes of the snail Littorina saxatilis divergent selection forms strong barriers to gene flow, while the role of postzygotic barriers due to selection against hybrids remains unclear. High embryo abortion rates in this species could indicate the presence of such barriers. Postzygotic barriers might include genetic incompatibilities (e.g. Dobzhansky-Muller incompatibilities) but also maladaptation, both expected to be most pronounced in contact zones. In addition, embryo abortion might reflect physiological stress on females and embryos independent of any genetic stress. We examined all embryos of >500 females sampled outside and inside contact zones of three populations in Sweden. Females' clutch size ranged from 0 to 1011 embryos (mean 130±123) and abortion rates varied between 0 and100% (mean 12%). We described female genotypes by using a hybrid index based on hundreds of SNPs differentiated between ecotypes with which we characterised female genotypes. We also calculated female SNP heterozygosity and inversion karyotype. Clutch size did not vary with female hybrid index and abortion rates were only weakly related to hybrid index in two sites but not at all in a third site. No additional variation in abortion rate was explained by female SNP heterozygosity, but increased female inversion heterozygosity added slightly to increased abortion. Our results show only weak and probably biologically insignificant postzygotic barriers contributing to ecotype divergence and the high and variable abortion rates were marginally, if at all, explained by hybrid index of females. AU - Johannesson, Kerstin AU - Zagrodzka, Zuzanna AU - Faria, Rui AU - Westram, Anja M AU - Butlin, Roger ID - 13067 TI - Data from: Is embryo abortion a postzygotic barrier to gene flow between Littorina ecotypes? ER -