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DCI: Learning Causal Differences between Gene Regulatory Networks [article]

Anastasiya Belyaeva, Chandler Squires, Caroline Uhler
2020 bioRxiv   pre-print
Here, we propose an algorithm that efficiently learns the differences in gene regulatory mechanisms between different conditions.  ...  AbstractSummaryDesigning interventions to control gene regulation necessitates modeling a gene regulatory network by a causal graph.  ...  We address this problem by noting that it is often of interest to learn changes in causal (regulatory) relationships between two related gene regulatory networks corresponding to different conditions,  ... 
doi:10.1101/2020.05.13.093765 fatcat:fljdkgeisjh3dfgvflw4zjyyw4

Direct Estimation of Differences in Causal Graphs [article]

Yuhao Wang, Chandler Squires, Anastasiya Belyaeva, Caroline Uhler
2018 arXiv   pre-print
This is of interest for example in genomics, where changes in the structure or edge weights of the underlying causal graphs reflect alterations in the gene regulatory networks.  ...  We here provide the first provably consistent method for directly estimating the differences in a pair of causal DAGs without separately learning two possibly large and dense DAG models and computing their  ...  directly learn the difference of two causal networks without having to estimate each network separately.  ... 
arXiv:1802.05631v3 fatcat:ca74znz3yzad3dcr3wxsspntfu

Scalable Causal Structure Learning: New Opportunities in Biomedicine [article]

Pulakesh Upadhyaya, Kai Zhang, Can Li, Xiaoqian Jiang, Yejin Kim
2021 arXiv   pre-print
This paper gives a practical tutorial on popular causal structure learning models with examples of real-world data to help healthcare audiences understand and apply them.  ...  We review prominent traditional, score-based and machine-learning based schemes for causal structure discovery, study some of their performance over some benchmark datasets, and discuss some of the applications  ...  It uses a method called Difference Causal Inference (DCI) and compares it to a difference-based GES as a baseline.  ... 
arXiv:2110.07785v1 fatcat:3dk2kfkvzjdqhazuenuhvg5f7e

The Multiple Dimensions of Networks in Cancer: A Perspective

Cristian Axenie, Roman Bauer, María Rodríguez Martínez
2021 Symmetry  
From agent-based modelling and mechano-biology to machine learning and predictive modelling, the perspective motivates a methodology well suited to mathematical and computational oncology and suggests  ...  It instigates the community to explore new paths and synergies under the umbrella of the Special Issue "Networks in Cancer: From Symmetry Breaking to Targeted Therapy".  ...  This includes gene regulatory networks, metabolic networks, and proteinprotein interactions (PPIs).  ... 
doi:10.3390/sym13091559 fatcat:tdlrnpbml5e3tjgpbicegn3mtu

Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology

Brittany Salazar, Emily Balczewski, Choong Ung, Shizhen Zhu
2016 International Journal of Molecular Sciences  
Computational strategies derived from big data science-network-and machine learning-based modeling and drug repositioning-hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma  ...  Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development.  ...  MNI was recently applied to decipher causal genes responsible for driving tumor progression in ductal carcinoma in situ (DCIS), a non-invasive lesion of breast cancer.  ... 
doi:10.3390/ijms18010037 pmid:28035989 pmcid:PMC5297672 fatcat:lyf4za4drzhbranotgao7334bi

Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

Alejandro Vazquez-Martin, Eugeni López-Bonetc, Sílvia Cufí, Cristina Oliveras-Ferraros, Sonia Del Barco, Begoña Martin-Castillo, Javier A. Menendez
2011 Drug resistance updates  
First, we describe a signalling network signature that overrides bioenergetics stress-and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions.  ...  Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin ("old drugs") to their recently recognized CSC targets ("new uses") within the network.  ...  A causal relationship between autophagy and cell survival in DCIS lesions has been illustrated by the fact that ATG6/Beclin-1 (a haploinsufficient tumour suppressor protein that is essential for autophagy  ... 
doi:10.1016/j.drup.2011.04.003 pmid:21600837 pmcid:PMC3742095 fatcat:vnuda22t2fepdij6wzaraawnta

Integrated Information as a Measure of Cognitive Processes in Coupled Genetic Repressilators

Luis Abrego, Alexey Zaikin
2019 Entropy  
In parallel, drawn originally from studies on neuroscience, integrated information proposes an approach to quantify the balance between integration and differentiation in the causal dynamics among the  ...  This conveys information processing from intracellular signaling networks enabling self-organization between other cells, typically involving mechanisms associated with cognitive systems.  ...  This is useful to the general picture of gene activation in regulatory networks, in which every gene switches between a high or low state in terms of the interplay of activation and inhibition of the chemical  ... 
doi:10.3390/e21040382 pmid:33267096 fatcat:dhitbmuvmjcybg6m66axktoq5u

Reconstructing the functional effect of TP53 somatic mutations on its regulon using causal signalling network modelling [article]

Charalampos Triantafyllidis, Alessandro Barberis, Ana Miar, Philip Chartlon, Fiona Hartley, Linda Van Bijsterveldt, Enio Gjerga, Julio Saez-Rodriguez, Francesca M Buffa
2022 bioRxiv   pre-print
Thus, to infer the impact of different TP53 mutations we compared the topological characteristics of the optimized and reconstructed (upwards of twenty thousand) gene networks.  ...  To address this, we first proceed with a machine learning (ML) approach, and then propose an integrated computational network modelling approach that reconstructs signalling networks using a comprehensive  ...  gene network approach enabling causal inference to reconstruct TP53 signalling networks in cancer samples and cell lines harbouring different TP53 mutations.  ... 
doi:10.1101/2022.06.23.497293 fatcat:wn2eux2adnh67ehwm63bktcb4q

Computational Medicine: Translating Models to Clinical Care

R. L. Winslow, N. Trayanova, D. Geman, M. I. Miller
2012 Science Translational Medicine  
Statistical learning is applied to high-dimensional biomolecular data to create models that describe relationships between molecules and networks.  ...  For example, when separating two disease phenotypes on the basis of a gene expression profile, a decision rule that is based on a regulatory pattern involving a small number of interacting genes can provide  ... 
doi:10.1126/scitranslmed.3003528 pmid:23115356 pmcid:PMC3618897 fatcat:3pzsoz3iyzdpvmtwqw6x6nlvtm

A Longitudinal Study of the Association between Mammographic Density and Gene Expression in Normal Breast Tissue

Helga Bergholtz, Tonje Gulbrandsen Lien, Giske Ursin, Marit Muri Holmen, Åslaug Helland, Therese Sørlie, Vilde Drageset Haakensen
2019 Journal of mammary gland biology and neoplasia  
We obtained biopsies from breasts of healthy women at two different time points several years apart and performed microarray gene expression analysis.  ...  We validated findings from our previous study; negative correlation between RBL1 and MD in post-menopausal women, indicating involvement of the TGFβ pathway.  ...  Availability of Data and Material Gene expression data for the samples from the previous study (MDG1) are deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number  ... 
doi:10.1007/s10911-018-09423-x pmid:30613869 fatcat:stt5ysdfkjhzpgkrnbkwr2jhy4

Systems virology: host-directed approaches to viral pathogenesis and drug targeting

G. Lynn Law, Marcus J. Korth, Arndt G. Benecke, Michael G. Katze
2013 Nature Reviews Microbiology  
In the past decade, tools have become available to chart a new course, one directed at obtaining comprehensive systems-level views of the host response and the interplay between virus and host.  ...  Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield  ...  Josset for generating the networks in figure 3 , and M. Heise and M. Ferris for providing the data used in box 3.  ... 
doi:10.1038/nrmicro3036 pmid:23728212 pmcid:PMC4028060 fatcat:yk674zd7hzevladttnwmdgrjdi

Panoptic View of Prognostic Models for Personalized Breast Cancer Management

Geetanjali Saini, Karuna Mittal, Padmashree Rida, Emiel A. M. Janssen, Keerthi Gogineni, Ritu Aneja
2019 Cancers  
This review summarizes the prognostic and predictive insights provided by commercially available gene expression-based tests and other multivariate or clinical -omics-based prognostic/predictive models  ...  patient subgroups delineated by these clinicopathologic characteristics, as currently used methodologies in diagnostic pathology lack the capability to discern deeper genotypic and subtler phenotypic differences  ...  DNA, RNA, proteomic, copy number variant, and other information can now be seamlessly woven together using sophisticated big data analytics to generate probabilistic causal networks, improving the chances  ... 
doi:10.3390/cancers11091325 pmid:31500225 pmcid:PMC6770520 fatcat:auwccqlugvevnliouxc3p7icvi

Zi Shen Wan Fang Attenuates Neuroinflammation and Cognitive Function Via Remodeling the Gut Microbiota in Diabetes-Induced Cognitive Impairment Mice

Jiangwei Shi, Jiangwei Shi, Qingsheng Yin, Lin Zhang, Yu Wu, Pengrong Yi, Mengqing Guo, Huhu Li, Liuyi Yuan, Zixuan Wang, Pengwei Zhuang, Pengwei Zhuang (+5 others)
2022 Frontiers in Pharmacology  
The DCI mice were randomly divided into the model group (DCI), the low- and high-ZSWF–dose groups (9.63 g/kg, 18.72 g/kg), the mixed antibiotic group (ABs), and the ZSWF combined with mixed antibiotic  ...  In addition, ZSWF reshaped the imbalanced gut microbiota in DCI mice by reversing the abundance changes of a wide range of intestinal bacteria at the phyla and genus levels.  ...  Furthermore, an antibiotic intervention was used to assess the possibility of a causal relation between ZSWF improving cognitive and gut microbiota.  ... 
doi:10.3389/fphar.2022.898360 pmid:35910371 pmcid:PMC9335489 doaj:24922726c0db405c928a1c43de060706 fatcat:2xbisbzuxjbgflvlixkakzqtpy

The econometrics of Bayesian graphical models: a review with financial application

Daniel Felix Ahelegbey
2016 The Journal of Network Theory in Finance  
This paper presents a state-of-the-art review on the interface between statistics and econometrics in the inference and application of Bayesian graphical models.  ...  Recent advances in empirical finance have shown that the adoption of network theory is critical in order to understand contagion and systemic vulnerabilities.  ...  Also, the rank difference is the difference between the rank on the GCnet and that on the BGnet.  ... 
doi:10.21314/jntf.2016.016 fatcat:csl76y3sc5ahbfsrqwmzjdzpsi

Proteome, Phosphoproteome, and Hydroxyproteome of Liver Mitochondria in Diabetic Rats at Early Pathogenic Stages

Wen-Jun Deng, Song Nie, Jie Dai, Jia-Rui Wu, Rong Zeng
2009 Molecular & Cellular Proteomics  
During the transition to T2D, mitochondria undergo extensive changes in gene expression and arrive at a new highly  ...  The onset of T2D results from complex interactions between genetic and environmental factors.  ...  FIG. 4 . 4 A, spectral counts of different mitochondrial proteins between replicates (rep.) and between different samples.  ... 
doi:10.1074/mcp.m900020-mcp200 pmid:19700791 pmcid:PMC2808256 fatcat:dqwryx6y6feoxhw2w5j55ispfi
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