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- Hernández-Orozco, S, et al.
(författare)
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Algorithmic Probability-Guided Machine Learning on Non-Differentiable Spaces
- 2020
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Ingår i: Frontiers in artificial intelligence. - : Frontiers Media SA. - 2624-8212. ; 3, s. 567356-
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Tidskriftsartikel (refereegranskat)abstract
- We show how complexity theory can be introduced in machine learning to help bring together apparently disparate areas of current research. We show that this model-driven approach may require less training data and can potentially be more generalizable as it shows greater resilience to random attacks. In an algorithmic space the order of its element is given by its algorithmic probability, which arises naturally from computable processes. We investigate the shape of a discrete algorithmic space when performing regression or classification using a loss function parametrized by algorithmic complexity, demonstrating that the property of differentiation is not required to achieve results similar to those obtained using differentiable programming approaches such as deep learning. In doing so we use examples which enable the two approaches to be compared (small, given the computational power required for estimations of algorithmic complexity). We find and report that 1) machine learning can successfully be performed on a non-smooth surface using algorithmic complexity; 2) that solutions can be found using an algorithmic-probability classifier, establishing a bridge between a fundamentally discrete theory of computability and a fundamentally continuous mathematical theory of optimization methods; 3) a formulation of an algorithmically directed search technique in non-smooth manifolds can be defined and conducted; 4) exploitation techniques and numerical methods for algorithmic search to navigate these discrete non-differentiable spaces can be performed; in application of the (a) identification of generative rules from data observations; (b) solutions to image classification problems more resilient against pixel attacks compared to neural networks; (c) identification of equation parameters from a small data-set in the presence of noise in continuous ODE system problem, (d) classification of Boolean NK networks by (1) network topology, (2) underlying Boolean function, and (3) number of incoming edges.
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- Hernandez-Orozco, S, et al.
(författare)
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Algorithmically probable mutations reproduce aspects of evolution, such as convergence rate, genetic memory and modularity
- 2018
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Ingår i: Royal Society open science. - : The Royal Society. - 2054-5703. ; 5:8, s. 180399-
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Tidskriftsartikel (refereegranskat)abstract
- Natural selection explains how life has evolved over millions of years from more primitive forms. The speed at which this happens, however, has sometimes defied formal explanations when based on random (uniformly distributed) mutations. Here, we investigate the application of a simplicity bias based on a natural but algorithmic distribution of mutations (no recombination) in various examples, particularly binary matrices, in order to compare evolutionary convergence rates. Results both on synthetic and on small biological examples indicate an accelerated rate when mutations are not statistically uniform butalgorithmically uniform. We show that algorithmic distributions can evolve modularity and genetic memory by preservation of structures when they first occur sometimes leading to an accelerated production of diversity but also to population extinctions, possibly explaining naturally occurring phenomena such as diversity explosions (e.g. the Cambrian) and massive extinctions (e.g. the End Triassic) whose causes are currently a cause for debate. The natural approach introduced here appears to be a better approximation to biological evolution than models based exclusively upon random uniform mutations, and it also approaches a formal version of open-ended evolution based on previous formal results. These results validate some suggestions in the direction that computation may be an equally important driver of evolution. We also show that inducing the method on problems of optimization, such as genetic algorithms, has the potential to accelerate convergence of artificial evolutionary algorithms.
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- Kannan, V, et al.
(författare)
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Conditional Disease Development extracted from Longitudinal Health Care Cohort Data using Layered Network Construction
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 26170-
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Tidskriftsartikel (refereegranskat)abstract
- Health care data holds great promise to be used in clinical decision support systems. However, frequent near-synonymous diagnoses recorded separately, as well as the sheer magnitude and complexity of the disease data makes it challenging to extract non-trivial conclusions beyond confirmatory associations from such a web of interactions. Here we present a systematic methodology to derive statistically valid conditional development of diseases. To this end we utilize a cohort of 5,512,469 individuals followed over 13 years at inpatient care, including data on disability pension and cause of death. By introducing a causal information fraction measure and taking advantage of the composite structure in the ICD codes, we extract an effective directed lower dimensional network representation (100 nodes and 130 edges) of our cohort. Unpacking composite nodes into bipartite graphs retrieves, for example, that individuals with behavioral disorders are more likely to be followed by prescription drug poisoning episodes, whereas women with leiomyoma were more likely to subsequently experience endometriosis. The conditional disease development represent putative causal relations, indicating possible novel clinical relationships and pathophysiological associations that have not been explored yet.
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- Khan, SA, et al.
(författare)
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scAEGAN: Unification of single-cell genomics data by adversarial learning of latent space correspondences
- 2023
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2, s. e0281315-
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Tidskriftsartikel (refereegranskat)abstract
- Recent progress in Single-Cell Genomics has produced different library protocols and techniques for molecular profiling. We formulate a unifying, data-driven, integrative, and predictive methodology for different libraries, samples, and paired-unpaired data modalities. Our design of scAEGAN includes an autoencoder (AE) network integrated with adversarial learning by a cycleGAN (cGAN) network. The AE learns a low-dimensional embedding of each condition, whereas the cGAN learns a non-linear mapping between the AE representations. We evaluate scAEGAN using simulated data and real scRNA-seq datasets, different library preparations (Fluidigm C1, CelSeq, CelSeq2, SmartSeq), and several data modalities as paired scRNA-seq and scATAC-seq. The scAEGAN outperforms Seurat3 in library integration, is more robust against data sparsity, and beats Seurat 4 in integrating paired data from the same cell. Furthermore, in predicting one data modality from another, scAEGAN outperforms Babel. We conclude that scAEGAN surpasses current state-of-the-art methods and unifies integration and prediction challenges.
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- Kiani, NA, et al.
(författare)
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Predictive Systems Toxicology
- 2018
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Ingår i: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer New York. - 1940-6029. ; 1800, s. 535-557
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Tidskriftsartikel (refereegranskat)
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- Kotelnikova, E, et al.
(författare)
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Signaling networks in MS: a systems-based approach to developing new pharmacological therapies
- 2015
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 21:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. Systems biology approaches that study pathway dysregulation should offer benefits by integrating molecular networks and dynamic models with current biological knowledge for understanding disease heterogeneity and response to therapy. In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors. Among the downstream molecules implicated are Jak/Stat, NF-Kb, ERK1/3, p38 or Jun/Fos. Together, these data suggest that MS is likely to be associated with abnormalities in apoptosis/cell death, microglia activation, blood-brain barrier functioning, immune responses, cytokine production, and/or oxidative stress, although which pathways contribute to the cascade of damage and can be modulated remains an open question. While current MS drugs target some of these pathways, others remain untouched. Here, we propose a pragmatic systems analysis approach that involves the large-scale extraction of processes and pathways relevant to MS. These data serve as a scaffold on which computational modeling can be performed to identify disease subgroups based on the contribution of different processes. Such an analysis, targeting these relevant MS-signaling pathways, offers the opportunity to accelerate the development of novel individual or combination therapies.
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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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