Cortical Circuitry Implementing Graphical Models

2009 ◽  
Vol 21 (11) ◽  
pp. 3010-3056 ◽  
Author(s):  
Shai Litvak ◽  
Shimon Ullman

In this letter, we develop and simulate a large-scale network of spiking neurons that approximates the inference computations performed by graphical models. Unlike previous related schemes, which used sum and product operations in either the log or linear domains, the current model uses an inference scheme based on the sum and maximization operations in the log domain. Simulations show that using these operations, a large-scale circuit, which combines populations of spiking neurons as basic building blocks, is capable of finding close approximations to the full mathematical computations performed by graphical models within a few hundred milliseconds. The circuit is general in the sense that it can be wired for any graph structure, it supports multistate variables, and it uses standard leaky integrate-and-fire neuronal units. Following previous work, which proposed relations between graphical models and the large-scale cortical anatomy, we focus on the cortical microcircuitry and propose how anatomical and physiological aspects of the local circuitry may map onto elements of the graphical model implementation. We discuss in particular the roles of three major types of inhibitory neurons (small fast-spiking basket cells, large layer 2/3 basket cells, and double-bouquet neurons), subpopulations of strongly interconnected neurons with their unique connectivity patterns in different cortical layers, and the possible role of minicolumns in the realization of the population-based maximum operation.

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 167 ◽  
Author(s):  
Qingyang Zhang

The nonparanormal graphical model has emerged as an important tool for modeling dependency structure between variables because it is flexible to non-Gaussian data while maintaining the good interpretability and computational convenience of Gaussian graphical models. In this paper, we consider the problem of detecting differential substructure between two nonparanormal graphical models with false discovery rate control. We construct a new statistic based on a truncated estimator of the unknown transformation functions, together with a bias-corrected sample covariance. Furthermore, we show that the new test statistic converges to the same distribution as its oracle counterpart does. Both synthetic data and real cancer genomic data are used to illustrate the promise of the new method. Our proposed testing framework is simple and scalable, facilitating its applications to large-scale data. The computational pipeline has been implemented in the R package DNetFinder, which is freely available through the Comprehensive R Archive Network.


2021 ◽  
Vol 17 (3) ◽  
pp. 1-33
Author(s):  
Beilun Wang ◽  
Jiaqi Zhang ◽  
Yan Zhang ◽  
Meng Wang ◽  
Sen Wang

Recently, the Internet of Things (IoT) receives significant interest due to its rapid development. But IoT applications still face two challenges: heterogeneity and large scale of IoT data. Therefore, how to efficiently integrate and process these complicated data becomes an essential problem. In this article, we focus on the problem that analyzing variable dependencies of data collected from different edge devices in the IoT network. Because data from different devices are heterogeneous and the variable dependencies can be characterized into a graphical model, we can focus on the problem that jointly estimating multiple, high-dimensional, and sparse Gaussian Graphical Models for many related tasks (edge devices). This is an important goal in many fields. Many IoT networks have collected massive multi-task data and require the analysis of heterogeneous data in many scenarios. Past works on the joint estimation are non-distributed and involve computationally expensive and complex non-smooth optimizations. To address these problems, we propose a novel approach: Multi-FST. Multi-FST can be efficiently implemented on a cloud-server-based IoT network. The cloud server has a low computational load and IoT devices use asynchronous communication with the server, leading to efficiency. Multi-FST shows significant improvement, over baselines, when tested on various datasets.


Complexity ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Qiang Tian ◽  
Rui Wang ◽  
Shijie Li ◽  
Wenjun Wang ◽  
Ou Wu ◽  
...  

Understanding and solving the psychological health problems of college students have become a focus of social attention. Complex networks have become important tools to study the factors affecting psychological health, and the Gaussian graphical model is often used to estimate psychological networks. However, previous studies leave some gaps to overcome, including the following aspects. (1) When studying networks of subpopulations, the estimation neglects the intrinsic relationships among subpopulations, leading to a large difference between the estimated network and the real network. (2) Because of the high cost, previous psychological surveys often have a small sample size, and the psychological description is insufficient. Here, the intrinsic connections among multiple tasks are used, and multitask machine learning is applied to develop a multitask Gaussian graphical model. The psychological networks of the population and subpopulations are estimated based on psychological questionnaire data. This study is the first to apply a psychological network to such a large-scale college student psychological analysis, and we obtain some interesting results. The model presented here is a dynamic model based on complex networks which predicts individual behavior and provides insight into the intrinsic links among various symptoms.


2019 ◽  
Author(s):  
Kyle Konze ◽  
Pieter Bos ◽  
Markus Dahlgren ◽  
Karl Leswing ◽  
Ivan Tubert-Brohman ◽  
...  

We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and cloud-based free energy calculations allows for large-scale potency predictions of compounds on a timescale that impacts drug discovery. The process is further accelerated by using a combination of population-based statistics and active learning techniques. Using this approach, we rapidly optimized R-groups and core hops for inhibitors of cyclin-dependent kinase 2. We explored greater than 300 thousand ideas and identified 35 ligands with diverse commercially available R-groups and a predicted IC<sub>50</sub> < 100 nM, and four unique cores with a predicted IC<sub>50</sub> < 100 nM. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns.


2019 ◽  
Author(s):  
Kyle Konze ◽  
Pieter Bos ◽  
Markus Dahlgren ◽  
Karl Leswing ◽  
Ivan Tubert-Brohman ◽  
...  

We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and cloud-based free energy calculations allows for large-scale potency predictions of compounds on a timescale that impacts drug discovery. The process is further accelerated by using a combination of population-based statistics and active learning techniques. Using this approach, we rapidly optimized R-groups and core hops for inhibitors of cyclin-dependent kinase 2. We explored greater than 300 thousand ideas and identified 35 ligands with diverse commercially available R-groups and a predicted IC<sub>50</sub> < 100 nM, and four unique cores with a predicted IC<sub>50</sub> < 100 nM. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns.


2021 ◽  
Vol 11 (6) ◽  
pp. 497
Author(s):  
Yoonsuk Jung ◽  
Eui Im ◽  
Jinhee Lee ◽  
Hyeah Lee ◽  
Changmo Moon

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78–0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83–0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61–0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.


Author(s):  
Krzysztof Jurczuk ◽  
Marcin Czajkowski ◽  
Marek Kretowski

AbstractThis paper concerns the evolutionary induction of decision trees (DT) for large-scale data. Such a global approach is one of the alternatives to the top-down inducers. It searches for the tree structure and tests simultaneously and thus gives improvements in the prediction and size of resulting classifiers in many situations. However, it is the population-based and iterative approach that can be too computationally demanding to apply for big data mining directly. The paper demonstrates that this barrier can be overcome by smart distributed/parallel processing. Moreover, we ask the question whether the global approach can truly compete with the greedy systems for large-scale data. For this purpose, we propose a novel multi-GPU approach. It incorporates the knowledge of global DT induction and evolutionary algorithm parallelization together with efficient utilization of memory and computing GPU’s resources. The searches for the tree structure and tests are performed simultaneously on a CPU, while the fitness calculations are delegated to GPUs. Data-parallel decomposition strategy and CUDA framework are applied. Experimental validation is performed on both artificial and real-life datasets. In both cases, the obtained acceleration is very satisfactory. The solution is able to process even billions of instances in a few hours on a single workstation equipped with 4 GPUs. The impact of data characteristics (size and dimension) on convergence and speedup of the evolutionary search is also shown. When the number of GPUs grows, nearly linear scalability is observed what suggests that data size boundaries for evolutionary DT mining are fading.


Gut ◽  
2021 ◽  
pp. gutjnl-2020-322545
Author(s):  
Han-Mo Chiu ◽  
Grace Hsiao-Hsuan Jen ◽  
Ying-Wei Wang ◽  
Jean Ching-Yuan Fann ◽  
Chen-Yang Hsu ◽  
...  

ObjectiveTo measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.DesignA prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.ResultsFIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).ConclusionA large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youn Young Park ◽  
Kil‑yong Lee ◽  
Seong Taek Oh ◽  
Sang Hyun Park ◽  
Kyung Do Han ◽  
...  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


2021 ◽  
Vol 22 (11) ◽  
pp. 5793
Author(s):  
Brianna M. Quinville ◽  
Natalie M. Deschenes ◽  
Alex E. Ryckman ◽  
Jagdeep S. Walia

Sphingolipids are a specialized group of lipids essential to the composition of the plasma membrane of many cell types; however, they are primarily localized within the nervous system. The amphipathic properties of sphingolipids enable their participation in a variety of intricate metabolic pathways. Sphingoid bases are the building blocks for all sphingolipid derivatives, comprising a complex class of lipids. The biosynthesis and catabolism of these lipids play an integral role in small- and large-scale body functions, including participation in membrane domains and signalling; cell proliferation, death, migration, and invasiveness; inflammation; and central nervous system development. Recently, sphingolipids have become the focus of several fields of research in the medical and biological sciences, as these bioactive lipids have been identified as potent signalling and messenger molecules. Sphingolipids are now being exploited as therapeutic targets for several pathologies. Here we present a comprehensive review of the structure and metabolism of sphingolipids and their many functional roles within the cell. In addition, we highlight the role of sphingolipids in several pathologies, including inflammatory disease, cystic fibrosis, cancer, Alzheimer’s and Parkinson’s disease, and lysosomal storage disorders.


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