Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features.
Cell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus. In addition to studying the network interactions, there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the varia...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-10-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4619640?pdf=render |
| _version_ | 1819023279554297856 |
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| author | Hirenkumar K Makadia James S Schwaber Rajanikanth Vadigepalli |
| author_facet | Hirenkumar K Makadia James S Schwaber Rajanikanth Vadigepalli |
| author_sort | Hirenkumar K Makadia |
| collection | DOAJ |
| description | Cell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus. In addition to studying the network interactions, there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the variability involved in cellular decision making. Previous studies have considered the information transfer between the signaling and transcriptional domains based on an instantaneous relationship between the molecular activities. These studies predict a limited binary on/off encoding mechanism which underestimates the complexity of biological information processing, and hence the utility of single cell resolution data. Here we pursue a novel strategy that reformulates the information transfer problem as involving dynamic features of signaling rather than molecular abundances. We pursue a computational approach to test if and how the transcriptional regulatory activity patterns can be informative of the temporal history of signaling. Our analysis reveals (1) the dynamic features of signaling that significantly alter transcriptional regulatory patterns (encoding), and (2) the temporal history of signaling that can be inferred from single cell scale snapshots of transcriptional activity (decoding). Immediate early gene expression patterns were informative of signaling peak retention kinetics, whereas transcription factor activity patterns were informative of activation and deactivation kinetics of signaling. Moreover, the information processing aspects varied across the network, with each component encoding a selective subset of the dynamic signaling features. We developed novel sensitivity and information transfer maps to unravel the dynamic multiplexing of signaling features at each of these network components. Unsupervised clustering of the maps revealed two groups that aligned with network motifs distinguished by transcriptional feedforward vs feedback interactions. Our new computational methodology impacts the single cell scale experiments by identifying downstream snapshot measures required for inferring specific dynamical features of upstream signals involved in the regulation of cellular responses. |
| first_indexed | 2024-12-21T04:36:22Z |
| format | Article |
| id | doaj.art-797fd023cdb64e05b7c1820f8d23cd65 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-21T04:36:22Z |
| publishDate | 2015-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-797fd023cdb64e05b7c1820f8d23cd652022-12-21T19:15:50ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582015-10-011110e100456310.1371/journal.pcbi.1004563Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features.Hirenkumar K MakadiaJames S SchwaberRajanikanth VadigepalliCell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus. In addition to studying the network interactions, there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the variability involved in cellular decision making. Previous studies have considered the information transfer between the signaling and transcriptional domains based on an instantaneous relationship between the molecular activities. These studies predict a limited binary on/off encoding mechanism which underestimates the complexity of biological information processing, and hence the utility of single cell resolution data. Here we pursue a novel strategy that reformulates the information transfer problem as involving dynamic features of signaling rather than molecular abundances. We pursue a computational approach to test if and how the transcriptional regulatory activity patterns can be informative of the temporal history of signaling. Our analysis reveals (1) the dynamic features of signaling that significantly alter transcriptional regulatory patterns (encoding), and (2) the temporal history of signaling that can be inferred from single cell scale snapshots of transcriptional activity (decoding). Immediate early gene expression patterns were informative of signaling peak retention kinetics, whereas transcription factor activity patterns were informative of activation and deactivation kinetics of signaling. Moreover, the information processing aspects varied across the network, with each component encoding a selective subset of the dynamic signaling features. We developed novel sensitivity and information transfer maps to unravel the dynamic multiplexing of signaling features at each of these network components. Unsupervised clustering of the maps revealed two groups that aligned with network motifs distinguished by transcriptional feedforward vs feedback interactions. Our new computational methodology impacts the single cell scale experiments by identifying downstream snapshot measures required for inferring specific dynamical features of upstream signals involved in the regulation of cellular responses.http://europepmc.org/articles/PMC4619640?pdf=render |
| spellingShingle | Hirenkumar K Makadia James S Schwaber Rajanikanth Vadigepalli Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features. PLoS Computational Biology |
| title | Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features. |
| title_full | Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features. |
| title_fullStr | Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features. |
| title_full_unstemmed | Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features. |
| title_short | Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features. |
| title_sort | intracellular information processing through encoding and decoding of dynamic signaling features |
| url | http://europepmc.org/articles/PMC4619640?pdf=render |
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