Abstract Background A feature common to all DNA sequencing technologies is the presence of base-call errors in the sequenced reads. The implications of such errors are application specific, ranging from minor informatics nuisances to major problems affecting biological inferences. Recently developed "next-gen" sequencing technologies have greatly reduced the cost of sequencing, but have been shown to be more error prone than previous technologies. Both position specific (depending on the location in the read) and sequence specific (depending on the sequence in the read) errors have been identified in Illumina and Life Technology sequencing platforms. We describe a new type of systematic error that manifests as statistically unlikely accumulations of errors at specific genome (or transcriptome) locations. Results We characterize and describe systematic errors using overlapping paired reads from high-coverage data. We show that such errors occur in approximately 1 in 1000 base pairs, and that they are highly replicable across experiments. We identify motifs that are frequent at systematic error sites, and describe a classifier that distinguishes heterozygous sites from systematic error. Our classifier is designed to accommodate data from experiments in which the allele frequencies at heterozygous sites are not necessarily 0.5 (such as in the case of RNA-Seq), and can be used with single-end datasets. Conclusions Systematic errors can easily be mistaken for heterozygous sites in individuals, or for SNPs in population analyses. Systematic errors are particularly problematic in low coverage experiments, or in estimates of allele-specific expression from RNA-Seq data. Our characterization of systematic error has allowed us to develop a program, called SysCall, for identifying and correcting such errors. We conclude that correction of systematic errors is important to consider in the design and interpretation of high-throughput sequencing experiments. <<<

Rachael B. Chanin, Patrick T. West, Jakob Wirbel, Matthew O. Gill, Gabriella Z. M. Green, Ryan M. Park, Nora Enright, Arjun M. Miklos, Angela S. Hickey, Erin F. Brooks, Krystal K. Lum, Ileana M. Cristea, Ami S. Bhatt <<<

We present a practical example for the phenomenon of color assimilation. We describe the advances in research on color assimilation from von Bezold, to Albers and Munker, and provide a compelling example of the recently described “Confetti-illusion” by Novick. Our research introduces a novel aspect by showing how unripe and greenish looking oranges can be perceived as ripe and vibrantly colored when viewed through an orange net. These findings highlight the significant implications of color assimilation in everyday consumer environments, offering a fresh perspective on how visual perception can be manipulated. <<<

Jonas Richiardi, Andre Altmann, Anna-Clare Milazzo, Catie Chang, M. Mallar Chakravarty, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Patricia Conrod, Mira Fauth-Bühler, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Penny Gowland, Andreas Heinz, Hervé Lemaître, Karl F. Mann, Jean-Luc Martinot, Frauke Nees, Tomáš Paus, Zdenka Pausova, Marcella Rietschel, Trevor W. Robbins, Michael N. Smolka, Rainer Spanagel, Andreas Ströhle, Gunter Schumann, Mike Hawrylycz, Jean-Baptiste Poline, Michael D. Greicius, , Lisa Albrecht, Chris Andrew, Mercedes Arroyo, Eric Artiges, Semiha Aydin, Christine Bach, Tobias Banaschewski, Alexis Barbot, Gareth Barker, Nathalie Boddaert, Arun Bokde, Zuleima Bricaud, Uli Bromberg, Ruediger Bruehl, Christian Büchel, Arnaud Cachia, Anna Cattrell, Patricia Conrod, Patrick Constant, Jeffrey Dalley, Benjamin Decideur, Sylvane Desrivieres, Tahmine Fadai, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Fanny Gollier Briand, Penny Gowland, Bert Heinrichs, Andreas Heinz, Nadja Heym, Thomas Hübner, James Ireland, Bernd Ittermann, Tianye Jia, Mark Lathrop, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Katharina Lüdemann, Christine Macare, Catherine Mallik, Jean-François Mangin, Karl Mann, Jean- Luc Martinot, Eva Mennigen, Fabiana Mesquita de Carvahlo, Xavier Mignon, Ruben Miranda, Kathrin Müller, Frauke Nees, Charlotte Nymberg, Marie-Laure Paillere, Tomas Paus, Zdenka Pausova, Jean-Baptiste Poline, Luise Poustka, Michael Rapp, Gabriel Robert, Jan Reuter, Marcella Rietschel, Stephan Ripke, Trevor Robbins, Sarah Rodehacke, John Rogers, Alexander Romanowski, Barbara Ruggeri, Christine Schmäl, Dirk Schmidt, Sophia Schneider, MarkGunter Schumann, Florian Schubert, Yannick Schwartz, Michael Smolka, Wolfgang Sommer, Rainer Spanagel, Claudia Speiser, Tade Spranger, Alicia Stedman, Sabina Steiner, Dai Stephens, Nicole Strache, Andreas Ströhle, Maren Struve, Naresh Subramaniam, Lauren Topper, Robert Whelan, Steve Williams, Juliana Yacubian, Monica Zilbovicius, C Peng Wong, Steven Lubbe, Lourdes Martinez-Medina, Alinda Fernandes, Amir Tahmasebi <<<

Cooperating brain regions express similar genesWhen the brain is at rest, a number of distinct areas are functionally connected. They tend to be organized in networks. Richiardiet al.compared brain imaging and gene expression data to build computational models of these networks. These functional networks are underpinned by the correlated expression of a core set of 161 genes. In this set, genes coding for ion channels and other synaptic functions such as neurotransmitter release dominate.Science, this issue p.1241 <<<

Huilin Wang, Zirui Dong, Rui Zhang, Matthew Hoi Kin Chau, Zhenjun Yang, Kathy Yin Ching Tsang, Hoi Kin Wong, Baoheng Gui, Zhuo Meng, Kelin Xiao, Xiaofan Zhu, Yanfang Wang, Shaoyun Chen, Tak Yeung Leung, Sau Wai Cheung, Yvonne K. Kwok, Cynthia C. Morton, Yuanfang Zhu, Kwong Wai Choy <<<

Breast cancer, the most prevalent malignancy in women, is also the leading cause of cancer-related deaths in women worldwide. The activation of the Wnt pathway plays a pivotal role in the metastatic abilities of breast cancer. In this study, IL1F6, MRGPRX1, and SEC14L3 were significantly correlated to breast cancer patients'overall survival based on TCGA-BRCA dataset. Although IL1F6, MRGPRX1 and SEC14L3 high expression were associated with better survival in breast cancer patients, SEC14L3 had the biggest survival benefit for breast cancer; therefore, SEC14L3 was selected for the subsequent investigation. SEC14L3 mRNA expression and protein levels within breast cancer cell lines decreased compared with normal human breast epithelial cells. Overexpressing SEC14L3 in breast cancer cells inhibited the malignant phenotypes of cancer cells, including the capacity of cells to migrate and invade. SEC14L3 overexpression decreased the levels of mesenchymal markers, whereas SEC14L3 knockdown facilitated the malignant behaviors of breast cancer cells. SEC14L3 overexpression also inhibited Wnt/β-catenin activation. The Wnt agonist strengthened the malignant phenotypes of breast cancer cells; moreover, the anti-tumor effects of SEC14L3 overexpression were partially attenuated by the Wnt agonist. Conclusively, SEC14L3, which is underexpressed in breast cancer cells and tissues, could play a tumor-suppressive role in a Wnt/β-catenin-related way. <<<

The hippocampus and entorhinal cortex have been linked to both memory functions and to spatial cognition, but it has been unclear how these ideas relate to each other. An important part of spatial cognition is the ability to keep track of a reference location using self-motion cues (sometimes referred to as path integration), and it has been suggested that the hippocampus or entorhinal cortex is essential for this ability. Patients with hippocampal lesions or larger lesions that also included entorhinal cortex were led on paths while blindfolded (up to 15 m in length) and were asked to actively maintain the path in mind. Patients pointed to and estimated their distance from the start location as accurately as controls. A rotation condition confirmed that performance was based on self-motion cues. When demands on long-term memory were increased, patients were impaired. Thus, in humans, the hippocampus and entorhinal cortex are not essential for path integration. <<<

Adolescence is a period of substantial social-emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain. <<<

The AlphaZero algorithm has been successfully applied in a range of discretedomains, most notably board games. It utilizes a neural network, that learns avalue and policy function to guide the exploration in a Monte-Carlo TreeSearch. Although many search improvements have been proposed for Monte-CarloTree Search in the past, most of them refer to an older variant of the UpperConfidence bounds for Trees algorithm that does not use a policy for planning.We introduce a new, improved search algorithm for AlphaZero which generalizesthe search tree to a directed acyclic graph. This enables information flowacross different subtrees and greatly reduces memory consumption. Along withMonte-Carlo Graph Search, we propose a number of further extensions, such asthe inclusion of Epsilon-greedy exploration, a revised terminal solver and theintegration of domain knowledge as constraints. In our evaluations, we use theCrazyAra engine on chess and crazyhouse as examples to show that these changesbring significant improvements to AlphaZero. <<<

Abstract We introduce unitary-gate randomized benchmarking (URB) for qudit gates by extending single- and multi-qubit URB to single- and multi-qudit gates. Specifically, we develop a qudit URB procedure that exploits unitary 2-designs. Furthermore, we show that our URB procedure is not simply extracted from the multi-qubit case by equating qudit URB to URB of the symmetric multi-qubit subspace. Our qudit URB is elucidated by using pseudocode, which facilitates incorporating into benchmarking applications. <<<

Andrew W. Senior, Richard Evans, John Jumper, James Kirkpatrick, Laurent Sifre, Tim Green, Chongli Qin, Augustin Žídek, Alexander W. R. Nelson, Alex Bridgland, Hugo Penedones, Stig Petersen, Karen Simonyan, Steve Crossan, Pushmeet Kohli, David T. Jones, David Silver, Koray Kavukcuoglu, Demis Hassabis <<<

The consolidation of discrete experiences into a coherent narrative shapes the cognitive map, providing structured mental representations of our experiences. In this process, past memories are reactivated and replayed in sequence, fostering hippocampal-cortical dialogue. However, brain-wide engagement coinciding with sequential reactivation (or replay) of memories remains largely unexplored. In this study, employing simultaneous EEG-fMRI, we capture both the spatial and temporal dynamics of memory replay. We find that during mental simulation, past memories are replayed in fast sequences as detected via EEG. These transient replay events are associated with heightened fMRI activity in the hippocampus and medial prefrontal cortex. Replay occurrence strengthens functional connectivity between the hippocampus and the default mode network, a set of brain regions key to representing the cognitive map. On the other hand, when subjects are at rest following learning, memory reactivation of task-related items is stronger than that of pre-learning rest, and is also associated with heightened hippocampal activation and augmented hippocampal connectivity to the entorhinal cortex. Together, our findings highlight a distributed, brain-wide engagement associated with transient memory reactivation and its sequential replay. <<<

AbstractWith the further transformation of The Large Sky Area Multi-Object Fiber Spectroscopic Telescope, the new generation of fiber positioner robot chooses a 4 mm hollow cup motor with minimum phase inductance. Because the load of the fiber positioner robot is constant and the inertia of the motor is very small, an open loop positioning control method based on Space Vector Pulse Width Modulation is proposed, and the specific open loop parameters are directly tuned by relevant experimental strategies. The critical factors of the open loop driving mode are discussed in detail from four aspects: subdivision, fundamental frequency, wave generation mode and peak current. Based on the actual fiber positioner robot, the hardware driver and assessment platform are built. The positioning tests show that the method proposed is practical and effective, and meets the precision positioning demand of the new generation optical fiber positioner robot. <<<

An essential prerequisite for evolution by natural selection is variation among individuals in traits that affect fitness. The ability of a system to produce selectable variation, known as evolvability, thus markedly affects the rate of evolution. Although the immune system is among the fastest-evolving components in mammals, the sources of variation in immune traits remain largely unknown. Here we show that an important determinant of the immune system's evolvability is its organization into interacting modules represented by different immune cell types. By profiling immune cell variation in bone marrow of 54 genetically diverse mouse strains from the Collaborative Cross, we found that variation in immune cell frequencies is polygenic and that many associated genes are involved in homeostatic balance through cell-intrinsic functions of proliferation, migration and cell death. However, we also found genes associated with the frequency of a particular cell type that are expressed in a different cell type, exerting their effect in what we term cyto-trans. The vertebrate evolutionary record shows that genes associated in cyto-trans have faced weaker negative selection, thus increasing the robustness and hence evolvability of the immune system. This phenomenon is similarly observable in human blood. Our findings suggest that interactions between different components of the immune system provide a phenotypic space in which mutations can produce variation with little detriment, underscoring the role of modularity in the evolution of complex systems. <<<

Michael S Haney, Róbert Pálovics, Christy Nicole Munson, Chris Long, Patrik K Johansson, Oscar Yip, Wentao Dong, Eshaan Rawat, Elizabeth West, Johannes C M Schlachetzki, Andy Tsai, Ian Hunter Guldner, Bhawika S Lamichhane, Amanda Smith, Nicholas Schaum, Kruti Calcuttawala, Andrew Shin, Yung-Hua Wang, Chengzhong Wang, Nicole Koutsodendris, Geidy E Serrano, Thomas G Beach, Eric M Reiman, Christopher K Glass, Monther Abu-Remaileh, Annika Enejder, Yadong Huang, Tony Wyss-Coray <<<

Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and Alzheimer's disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer's disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer's disease having the APOE4/4 genotype. In human induced pluripotent stem cell-derived microglia, fibrillar Aβ induces ACSL1 expression, triglyceride synthesis and lipid droplet accumulation in an APOE-dependent manner. Additionally, conditioned media from lipid droplet-containing microglia lead to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for Alzheimer's disease with microglial lipid droplet accumulation and neurotoxic microglia-derived factors, potentially providing therapeutic strategies for Alzheimer's disease. <<<

Wenkang Chen, Lu Chen, Xuan Zhang, Ning Yang, Jianghua Guo, Min Wang, Shenghui Ji, Xiangyu Zhao, Pengfei Yin, Lichun Cai, Jing Xu, Lili Zhang, Yingjia Han, Yingni Xiao, Gen Xu, Yuebin Wang, Shuhui Wang, Sheng Wu, Fang Yang, David Jackson, Jinkui Cheng, Saihua Chen, Chuanqing Sun, Feng Qin, Feng Tian, Alisdair R. Fernie, Jiansheng Li, Jianbing Yan, Xiaohong Yang <<<

A better understanding of the extent of convergent selection among crops could greatly improve breeding programs. We found that the quantitative trait locus KRN2 in maize and its rice ortholog, OsKRN2 , experienced convergent selection. These orthologs encode WD40 proteins and interact with a gene of unknown function, DUF1644, to negatively regulate grain number in both crops. Knockout of KRN2 in maize or OsKRN2 in rice increased grain yield by ~10% and ~8%, respectively, with no apparent trade-offs in other agronomic traits. Furthermore, genome-wide scans identified 490 pairs of orthologous genes that underwent convergent selection during maize and rice evolution, and these were enriched for two shared molecular pathways. KRN2 , together with other convergently selected genes, provides an excellent target for future crop improvement. <<<