Inference of chromosome-specific copy numbers using population haplotypes

<p>Abstract</p> <p>Background</p> <p>Using microarray and sequencing platforms, a large number of copy number variations (CNVs) have been identified in humans. In practice, because our human genome is a diploid, these platforms are limited to or more accurate for detecting total copy numbers rather than chromosome-specific copy numbers at each of the two homologous chromosomes. Nevertheless, the analysis of linkage disequilibrium (LD) between CNVs and SNPs indicates that distinct copy numbers often sit on their own background haplotypes.</p> <p>Results</p> <p>We propose new computational models for inferring chromosome-specific copy numbers by distinguishing background haplotypes of each copy number. The formulated problems are shown to be NP-hard and approximation/heuristic algorithms are developed. Simulation indicates that our method is accurate and outperforms the existing approach. By testing the program in 60 parent-offspring trios, the inferred chromosome-specific copy numbers are highly consistent with the law of Mendelian inheritance. The distributions of copy numbers at chromosomal level are provided for 270 individuals in three HapMap panels.</p> <p>Conclusions</p> <p>The estimation of chromosome-specific copy numbers using microarray or sequencing platforms was often confounded by a number of factors. This study showed that the integration of background haplotypes is able to improve the accuracies of copy number estimation at chromosome level, especially for the CNVs having strong LD with SNPs in proximity.</p

Accelerating and Improving AlphaZero Using Population Based Training

AlphaZero has been very successful in many games. Unfortunately, it still consumes a huge amount of computing resources, the majority of which is spent in self-play. Hyperparameter tuning exacerbates the training cost since each hyperparameter configuration requires its own time to train one run, during which it will generate its own self-play records. As a result, multiple runs are usually needed for different hyperparameter configurations. This paper proposes using population based training (PBT) to help tune hyperparameters dynamically and improve strength during training time. Another significant advantage is that this method requires a single run only, while incurring a small additional time cost, since the time for generating self-play records remains unchanged though the time for optimization is increased following the AlphaZero training algorithm. In our experiments for 9x9 Go, the PBT method is able to achieve a higher win rate for 9x9 Go than the baselines, each with its own hyperparameter configuration and trained individually. For 19x19 Go, with PBT, we are able to obtain improvements in playing strength. Specifically, the PBT agent can obtain up to 74% win rate against ELF OpenGo, an open-source state-of-the-art AlphaZero program using a neural network of a comparable capacity. This is compared to a saturated non-PBT agent, which achieves a win rate of 47% against ELF OpenGo under the same circumstances.Comment: accepted by AAAI2020 as oral presentation. In this version, supplementary materials are adde

Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau.

While a number of genome-wide association studies have identified microtubule-associated protein tau as a strong risk factor for Parkinson's disease (PD), little is known about the mechanism through which human tau can predispose an individual to this disease. Here, we demonstrate that expression of human wild-type tau is sufficient to disrupt the survival of dopaminergic neurons in a Drosophila model. Tau triggers a synaptic pathology visualized by vesicular monoamine transporter-pHGFP that precedes both the age-dependent formation of tau-containing neurofibrillary tangle-like pathology and the progressive loss of DA neurons, thereby recapitulating the pathological hallmarks of PD. Flies overexpressing tau also exhibit progressive impairments of both motor and learning behaviors. Surprisingly, contrary to common belief that hyperphosphorylated tau could aggravate toxicity, DA neuron degeneration is alleviated by expressing the modified, hyperphosphorylated tau(E14). Together, these results show that impairment of VMAT-containing synaptic vesicle, released to synapses before overt tauopathy may be the underlying mechanism of tau-associated PD and suggest that correction or prevention of this deficit may be appropriate targets for early therapeutic intervention

A Local-Pattern Related Look-Up Table

This paper describes a Relevance-Zone pattern table (RZT) that can be used to replace a traditional transposition table. An RZT stores exact game values for patterns that are discovered during a Relevance-Zone-Based Search (RZS), which is the current state-of-the-art in solving L&D problems in Go. Positions that share the same pattern can reuse the same exact game value in the RZT. The pattern matching scheme for RZTs is implemented using a radix tree, taking into consideration patterns with different shapes. To improve the efficiency of table lookups, we designed a heuristic that prevents redundant lookups. The heuristic can safely skip previously queried patterns for a given position, reducing the overhead to 10% of the original cost. We also analyze the time complexity of the RZT both theoretically and empirically. Experiments show the overhead of traversing the radix tree in practice during lookup remain flat logarithmically in relation to the number of entries stored in the table. Experiments also show that the use of an RZT instead of a traditional transposition table significantly reduces the number of searched nodes on two data sets of 7x7 and 19x19 L&D Go problems.Comment: Submitted to IEEE Transactions on Games (under review

Carbon Sequestration by Fruit Trees - Chinese Apple Orchards as an Example

Apple production systems are an important component in the Chinese agricultural sector with 1.99 million ha plantation. The orchards in China could play an important role in the carbon (C) cycle of terrestrial ecosystems and contribute to C sequestration. The carbon sequestration capability in apple orchards was analyzed through identifying a set of potential assessment factors and their weighting factors determined by a field model study and literature. The dynamics of the net C sink in apple orchards in China was estimated based on the apple orchard inventory data from 1990s and the capability analysis. The field study showed that the trees reached the peak of C sequestration capability when they were 18 years old, and then the capability began to decline with age. Carbon emission derived from management practices would not be compensated through C storage in apple trees before reaching the mature stage. The net C sink in apple orchards in China ranged from 14 to 32 Tg C, and C storage in biomass from 230 to 475 Tg C between 1990 and 2010. The estimated net C sequestration in Chinese apple orchards from 1990 to 2010 was equal to 4.5% of the total net C sink in the terrestrial ecosystems in China. Therefore, apple production systems can be potentially considered as C sinks excluding the energy associated with fruit production in addition to provide fruits