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BACKGROUND: Detection of DNA copy number alterations (CNAs) is critical to understand genetic diversity, genome evolution and pathological conditions such as cancer. Cancer genomes are plagued with widespread multi-level structural aberrations of chromosomes that pose challenges to discover CNAs of different length scales, and distinct biological origins and functions. Although several computational tools are available to identify CNAs using read depth (RD) signal, they fail to distinguish between large-scale and focal alterations due to inaccurate modeling of the RD signal of cancer genomes. Additionally, RD signal is affected by overdispersion-driven biases at low coverage, which significantly inflate false detection of CNA regions. RESULTS: We have developed CNAtra framework to hierarchically discover and classify 'large-scale' and 'focal' copy number gain/loss from a single whole-genome sequencing (WGS) sample. CNAtra first utilizes a multimodal-based distribution to estimate the copy number (CN) reference from the complex RD profile of the cancer genome. We implemented Savitzky-Golay smoothing filter and Modified Varri segmentation to capture the change points of the RD signal. We then developed a CN state-driven merging algorithm to identify the large segments with distinct copy numbers. Next, we identified focal alterations in each large segment using coverage-based thresholding to mitigate the adverse effects of signal variations. Using cancer cell lines and patient datasets, we confirmed CNAtra's ability to detect and distinguish the segmental aneuploidies and focal alterations. We used realistic simulated data for benchmarking the performance of CNAtra against other single-sample detection tools, where we artificially introduced CNAs in the original cancer profiles. We found that CNAtra is superior in terms of precision, recall and f-measure. CNAtra shows the highest sensitivity of 93 and 97% for detecting large-scale and focal alterations respectively. Visual inspection of CNAs revealed that CNAtra is the most robust detection tool for low-coverage cancer data. CONCLUSIONS: CNAtra is a single-sample CNA detection tool that provides an analytical and visualization framework for CNA profiling without relying on any reference control. It can detect chromosome-level segmental aneuploidies and high-confidence focal alterations, even from low-coverage data. CNAtra is an open-source software implemented in MATLAB®. It is freely available at https://github.com/AISKhalil/CNAtra.
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Algoritmos , Variações do Número de Cópias de DNA/genética , Neoplasias/genética , Sequenciamento Completo do Genoma/métodos , HumanosRESUMO
BACKGROUND: Hi-C and its variant techniques have been developed to capture the spatial organization of chromatin. Normalization of Hi-C contact map is essential for accurate modeling and interpretation of high-throughput chromatin conformation capture (3C) experiments. Hi-C correction tools were originally developed to normalize systematic biases of karyotypically normal cell lines. However, a vast majority of available Hi-C datasets are derived from cancer cell lines that carry multi-level DNA copy number variations (CNVs). CNV regions display over- or under-representation of interaction frequencies compared to CN-neutral regions. Therefore, it is necessary to remove CNV-driven bias from chromatin interaction data of cancer cell lines to generate a euploid-equivalent contact map. RESULTS: We developed the HiCNAtra framework to compute high-resolution CNV profiles from Hi-C or 3C-seq data of cancer cell lines and to correct chromatin contact maps from systematic biases including CNV-associated bias. First, we introduce a novel 'entire-fragment' counting method for better estimation of the read depth (RD) signal from Hi-C reads that recapitulates the whole-genome sequencing (WGS)-derived coverage signal. Second, HiCNAtra employs a multimodal-based hierarchical CNV calling approach, which outperformed OneD and HiNT tools, to accurately identify CNVs of cancer cell lines. Third, incorporating CNV information with other systematic biases, HiCNAtra simultaneously estimates the contribution of each bias and explicitly corrects the interaction matrix using Poisson regression. HiCNAtra normalization abolishes CNV-induced artifacts from the contact map generating a heatmap with homogeneous signal. When benchmarked against OneD, CAIC, and ICE methods using MCF7 cancer cell line, HiCNAtra-corrected heatmap achieves the least 1D signal variation without deforming the inherent chromatin interaction signal. Additionally, HiCNAtra-corrected contact frequencies have minimum correlations with each of the systematic bias sources compared to OneD's explicit method. Visual inspection of CNV profiles and contact maps of cancer cell lines reveals that HiCNAtra is the most robust Hi-C correction tool for ameliorating CNV-induced bias. CONCLUSIONS: HiCNAtra is a Hi-C-based computational tool that provides an analytical and visualization framework for DNA copy number profiling and chromatin contact map correction of karyotypically abnormal cell lines. HiCNAtra is an open-source software implemented in MATLAB and is available at https://github.com/AISKhalil/HiCNAtra .
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Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Neoplasias/patologia , Cromatina/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Células MCF-7 , Neoplasias/genética , Interface Usuário-ComputadorRESUMO
The ability to perceive color by the retina can be attributed to both its trichromatic photoreceptors and the antagonistic neural wiring known as the opponent process. While neuromorphic sensors have been shown to demonstrate memory and adaptation capabilities, color perception is still challenging due to the intrinsic lack of spectral selectivity in narrow bandgap semiconductors. Furthermore, research on emulating neural wiring is severely lacking. The combination of halide perovskite materials with a tunable bandgap and a novel bipolar photodetector design emulates the efficiency of the retina in processing color information. The stimuli-responsive material is also responsible for maintaining partial color constancy-an adaptation feature. Leveraging the unique enhancement of color contrasts, an in-sensor data compression and edge detection can also be demonstrated. The color perception, chromatic adaptation, and color contrast enhancement make perovskite bipolar photodetectors a unique example where the sensor and neural wiring can be co-developed in conjunction.
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In this paper, we propose an efficient quantum carry-lookahead adder based on the higher radix structure. For the addition of two n-bit numbers, our adder uses [Formula: see text] qubits and [Formula: see text] T gates to get the correct answer in T-depth [Formula: see text], where r is the radix. Quantum carry-lookahead adder has already attracted some attention because of its low T-depth. Our work further reduces the overall cost by introducing a higher radix layer. By analyzing the performance in T-depth, T-count, and qubit count, it is shown that the proposed adder is superior to existing quantum carry-lookahead adders. Even compared to the Draper out-of-place adder which is very compact and efficient, our adder is still better in terms of T-count.
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The modern-day computing technologies are continuously undergoing a rapid changing landscape; thus, the demands of new memory types are growing that will be fast, energy efficient and durable. The limited scaling capabilities of the conventional memory technologies are pushing the limits of data-intense applications beyond the scope of silicon-based complementary metal oxide semiconductors (CMOS). Resistive random access memory (RRAM) is one of the most suitable emerging memory technologies candidates that have demonstrated potential to replace state-of-the-art integrated electronic devices for advanced computing and digital and analog circuit applications including neuromorphic networks. RRAM has grown in prominence in the recent years due to its simple structure, long retention, high operating speed, ultra-low-power operation capabilities, ability to scale to lower dimensions without affecting the device performance and the possibility of three-dimensional integration for high-density applications. Over the past few years, research has shown RRAM as one of the most suitable candidates for designing efficient, intelligent and secure computing system in the post-CMOS era. In this manuscript, the journey and the device engineering of RRAM with a special focus on the resistive switching mechanism are detailed. This review also focuses on the RRAM based on two-dimensional (2D) materials, as 2D materials offer unique electrical, chemical, mechanical and physical properties owing to their ultrathin, flexible and multilayer structure. Finally, the applications of RRAM in the field of neuromorphic computing are presented.
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BACKGROUND: The revolution in next-generation sequencing (NGS) technology has allowed easy access and sharing of high-throughput sequencing datasets of cancer cell lines and their integrative analyses. However, long-term passaging and culture conditions introduce high levels of genomic and phenotypic diversity in established cell lines resulting in strain differences. Thus, clonal variation in cultured cell lines with respect to the reference standard is a major barrier in systems biology data analyses. Therefore, there is a pressing need for a fast and entry-level assessment of clonal variations within cell lines using their high-throughput sequencing data. RESULTS: We developed a Python-based software, AStra, for de novo estimation of the genome-wide segmental aneuploidy to measure and visually interpret strain-level similarities or differences of cancer cell lines from whole-genome sequencing (WGS). We demonstrated that aneuploidy spectrum can capture the genetic variations in 27 strains of MCF7 breast cancer cell line collected from different laboratories. Performance evaluation of AStra using several cancer sequencing datasets revealed that cancer cell lines exhibit distinct aneuploidy spectra which reflect their previously-reported karyotypic observations. Similarly, AStra successfully identified large-scale DNA copy number variations (CNVs) artificially introduced in simulated WGS datasets. CONCLUSIONS: AStra provides an analytical and visualization platform for rapid and easy comparison between different strains or between cell lines based on their aneuploidy spectra solely using the raw BAM files representing mapped reads. We recommend AStra for rapid first-pass quality assessment of cancer cell lines before integrating scientific datasets that employ deep sequencing. AStra is an open-source software and is available at https://github.com/AISKhalil/AStra.
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Recently, a great deal of scientific endeavour has been devoted to developing spin-based neuromorphic platforms owing to the ultra-low-power benefits offered by spin devices and the inherent correspondence between spintronic phenomena and the desired neuronal, synaptic behavior. While domain wall motion-based threshold activation unit has previously been demonstrated for neuromorphic circuits, it remains well known that neurons with threshold activation cannot completely learn nonlinearly separable functions. This paper addresses this fundamental limitation by proposing a novel domain wall motion-based dual-threshold activation unit with additional nonlinearity in its function. Furthermore, a new learning algorithm is formulated for a neuron with this activation function. We perform 100 trials of tenfold training and testing of our neural networks on real-world datasets taken from the UCI machine learning repository. On an average, the proposed algorithm achieves [Formula: see text] lower misclassification rate (MCR) than the traditional perceptron learning algorithm. In a circuit-level simulation, the neural networks with the proposed activation unit are observed to outperform the perceptron networks by as much as [Formula: see text] MCR. The energy consumption of a neuron having the proposed domain wall motion-based activation unit averages to [Formula: see text] approximately.
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Modelos Neurológicos , Redes Neurais de Computação , Algoritmos , Bases de Dados Factuais , Desenho de Equipamento , Humanos , Neurônios/fisiologiaRESUMO
Among emerging non-volatile storage technologies, redox-based resistive switching Random Access Memory (ReRAM) is a prominent one. The realization of Boolean logic functionalities using ReRAM adds an extra edge to this technology. Recently, 7-state ReRAM devices were used to realize ternary arithmetic circuits, which opens up the computing space beyond traditional binary values. In this manuscript, we report realization of multi-valued and fuzzy logic operators with a representative application using ReRAM devices. Multi-valued logic (MVL), such as Lukasiewicz logic generalizes Boolean logic by allowing more than two truth values. MVL also permits operations on fuzzy sets, where, in contrast to standard crisp logic, an element is permitted to have a degree of membership to a given set. Fuzzy operations generally model human reasoning better than Boolean logic operations, which is predominant in current computing technologies. When the available information for the modelling of a system is imprecise and incomplete, fuzzy logic provides an excellent framework for the system design. Practical applications of fuzzy logic include, industrial control systems, robotics, and in general, design of expert systems through knowledge-based reasoning. Our experimental results show, for the first time, that it is possible to model fuzzy logic natively using multi-state memristive devices.
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Redox-based resistive switching random access memory (ReRAM) offers excellent properties to implement future non-volatile memory arrays. Recently, the capability of two-state ReRAMs to implement Boolean logic functionality gained wide interest. Here, we report on seven-states Tantalum Oxide Devices, which enable the realization of an intrinsic modular arithmetic using a ternary number system. Modular arithmetic, a fundamental system for operating on numbers within the limit of a modulus, is known to mathematicians since the days of Euclid and finds applications in diverse areas ranging from e-commerce to musical notations. We demonstrate that multistate devices not only reduce the storage area consumption drastically, but also enable novel in-memory operations, such as computing using high-radix number systems, which could not be implemented using two-state devices. The use of high radix number system reduces the computational complexity by reducing the number of needed digits. Thus the number of calculation operations in an addition and the number of logic devices can be reduced.