Cerulean: A hybrid assembly using high throughput short and long reads

Genome assembly using high throughput data with short reads, arguably, remains an unresolvable task in repetitive genomes, since when the length of a repeat exceeds the read length, it becomes difficult to unambiguously connect the flanking regions. The emergence of third generation sequencing (Pacific Biosciences) with long reads enables the opportunity to resolve complicated repeats that could not be resolved by the short read data. However, these long reads have high error rate and it is an uphill task to assemble the genome without using additional high quality short reads. Recently, Koren et al. 2012 proposed an approach to use high quality short reads data to correct these long reads and, thus, make the assembly from long reads possible. However, due to the large size of both dataset (short and long reads), error-correction of these long reads requires excessively high computational resources, even on small bacterial genomes. In this work, instead of error correction of long reads, we first assemble the short reads and later map these long reads on the assembly graph to resolve repeats. Contribution: We present a hybrid assembly approach that is both computationally effective and produces high quality assemblies. Our algorithm first operates with a simplified version of the assembly graph consisting only of long contigs and gradually improves the assembly by adding smaller contigs in each iteration. In contrast to the state-of-the-art long reads error correction technique, which requires high computational resources and long running time on a supercomputer even for bacterial genome datasets, our software can produce comparable assembly using only a standard desktop in a short running time.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Discovery and genotyping of structural variation from long-read haploid genome sequence data

In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid human genomes. By using an assembly-based approach (SMRT-SV), we systematically assessed each genome independently for structural variants (SVs) and indels resolving the sequence structure of 461,553 genetic variants from 2 bp to 28 kbp in length. We find that &gt;89% of these variants have been missed as part of analysis of the 1000 Genomes Project even after adjusting for more common variants (MAF &gt; 1%). We estimate that this theoretical human diploid differs by as much as ∼16 Mbp with respect to the human reference, with long-read sequencing data providing a fivefold increase in sensitivity for genetic variants ranging in size from 7 bp to 1 kbp compared with short-read sequence data. Although a large fraction of genetic variants were not detected by short-read approaches, once the alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped in short-read sequence data sets with high accuracy. Uncoupling discovery from genotyping thus allows for the majority of this missed common variation to be genotyped in the human population. Interestingly, when we repeat SV detection on a pseudodiploid genome constructed in silico by merging the two haploids, we find that ∼59% of the heterozygous SVs are no longer detected by SMRT-SV. These results indicate that haploid resolution of long-read sequencing data will significantly increase sensitivity of SV detection.</jats:p

Computational and Biological Analogies for Understanding Fine-Tuned Parameters in Physics

In this philosophical paper, we explore computational and biological analogies to address the fine-tuning problem in cosmology. We first clarify what it means for physical constants or initial conditions to be fine-tuned. We review important distinctions such as the dimensionless and dimensional physical constants, and the classification of constants proposed by Levy-Leblond. Then we explore how two great analogies, computational and biological, can give new insights into our problem. This paper includes a preliminary study to examine the two analogies. Importantly, analogies are both useful and fundamental cognitive tools, but can also be misused or misinterpreted. The idea that our universe might be modelled as a computational entity is analysed, and we discuss the distinction between physical laws and initial conditions using algorithmic information theory. Smolin introduced the theory of "Cosmological Natural Selection" with a biological analogy in mind. We examine an extension of this analogy involving intelligent life. We discuss if and how this extension could be legitimated. Keywords: origin of the universe, fine-tuning, physical constants, initial conditions, computational universe, biological universe, role of intelligent life, cosmological natural selection, cosmological artificial selection, artificial cosmogenesis.Comment: 25 pages, Foundations of Science, in pres

Error threshold in optimal coding, numerical criteria and classes of universalities for complexity

The free energy of the Random Energy Model at the transition point between ferromagnetic and spin glass phases is calculated. At this point, equivalent to the decoding error threshold in optimal codes, free energy has finite size corrections proportional to the square root of the number of degrees. The response of the magnetization to the ferromagnetic couplings is maximal at the values of magnetization equal to half. We give several criteria of complexity and define different universality classes. According to our classification, at the lowest class of complexity are random graph, Markov Models and Hidden Markov Models. At the next level is Sherrington-Kirkpatrick spin glass, connected with neuron-network models. On a higher level are critical theories, spin glass phase of Random Energy Model, percolation, self organized criticality (SOC). The top level class involves HOT design, error threshold in optimal coding, language, and, maybe, financial market. Alive systems are also related with the last class. A concept of anti-resonance is suggested for the complex systems.Comment: 17 page

Rotation-disk connection for very low mass and substellar objects in the Orion Nebula Cluster

Angular momentum loss requires magnetic interaction between the forming star and both the circumstellar disk and the magnetically driven outflows. In order to test these predictions many authors have investigated a rotation-disk connection in pre-main sequence objects with masses larger than about 0.4Msun. For brown dwarfs this connection was not investigated as yet because there are very few samples available. We aim to extend this investigation well down into the substellar regime for our large sample of BDs in the Orion Nebula Cluster, for which we have recently measured rotational periods. In order to investigate a rotation-disk correlation, we derived near-infrared (NIR) excesses for a sample of 732 periodic variables in the Orion Nebula Cluster with masses ranging between 1.5-0.02 Msun and whose IJHK colors are available. Circumstellar NIR excesses were derived from the Delta[I-K] index. We performed our analysis in three mass bins.We found a rotation-disk correlation in the high and intermediate mass regime, in which objects with NIR excess tend to rotate slower than objects without NIR excess. Interestingly, we found no correlation in the substellar regime. A tight correlation between the peak-to-peak (ptp) amplitude of the rotational modulation and the NIR excess was found however for all objects with available ptp values. We discuss possible scenarios which may explain the lack of rotation-disk connection in the substellar mass regime. One possible reason could be the strong dependence of the mass accretion rate on stellar mass in the investigated mass range.Comment: 12 pages, 7 figures, accepted for publication "Astronomy and Astrophysics

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

Neurocognitive Interactions Between Anticipatory Anxiety and Memory Encoding

Although acute anxiety has been shown to improve encoding of threat-relevant information, its effects on threat-neutral information are less understood. Recent research suggests that anxiety can impair subsequent recall for neutral words, particularly following practice with the recall task. Here we use event-related potentials (ERPs) to test the notion that anxiety specifically disrupts the implementation of encoding strategies—such as elaborative encoding—that tend to develop with practice. ERPs were recorded as participants studied two sets of neutral words, one of which was presented in a stressful context using the threat-of-shock paradigm (threat block), and the other in a non-threatening context (safe block). A free recall test followed each block. As predicted, analyses of ERPs during study revealed that, relative to safe blocks, words studied during threat blocks evoked: 1) larger N400 amplitudes, consistent with impeded access to meaning, and 2) smaller amplitudes of a slow frontal positivity linked to elaborative encoding. The latter of these effects was selective to participants who received the threat block after the safe block, consistent with a dependence on task practice. In contrast to our previous work, we did not find differences in recall between conditions. However, exploratory analyses revealed that observed ERP differences were largest in those participants who recalled fewer words during threat than safe blocks. Overall, these data are consistent with models of acute anxiety that posit impairments to goal-directed internal attention, and further demonstrate their applicability to episodic memory encoding

Seasonal distribution of genetic types of planktonic foraminifer morphospecies in the Santa Barbara Channel and its paleoceanographic implications

We present data on the temporal distribution of planktonic foraminifer genotypes (small subunit (SSU) ribosomal (r) RNA gene) and morphospecies (sediment traps) collected during 1999 in the Santa Barbara Channel. The sampling was undertaken with special emphasis on paleoceanographically important morphospecies, predominantly Globigerina bulloides. We found the same genotype of G. bulloides (type IId) in all the changing hydrographic regimes associated with this region throughout the annual cycle with the exception of January, when we recorded the additional presence of the high-latitude G. bulloides type IIa. We identified three new genotypes: Neogloboquadrina dutertrei type Ic, N. pachyderma dextral type II, and Turborotalita quinqueloba type IId. Our data suggest that G. bulloides type IId and possibly even the new genotypes listed above may be associated specifically with the complex hydrography or other environmental features characteristic of this area. Since G. bulloides type IId occurs throughout the year and its peak fluxes are related to different hydrographic regimes, we argue that the physical properties of the water column are not the major factor influencing the distribution and growth of this genotype. In sediment trap samples we found a skewed coiling ratio for G. bulloides (most likely representing type IId), which is related neither to sea surface temperature nor to genotypic difference. This study illustrates the necessity to map both the spatial and temporal distribution of the genetic types, especially in areas of paleoceanographic interest, where geochemical and paleontological proxies are being calibrated

Radio Astronomy

Contains research objectives, summary of research and reports on five research projects.National Aeronautics and Space Administration (Grant NGL 22-009-016)National Aeronautics and Space Administration (Grant NGR 22-009-421)Langley Research Center Contract NASI-10693National Science Foundation (Grants GP-20769)National Science Foundation (Grants GP-21348)National Science Foundation (Grants GP-14589)California Institute of Technology Contract 952568Sloan Fund for Basic Research (M.I.T., Grant 241