Modelling transcriptional regulation using Gaussian Processes

Neil D. Lawrence, Guido Sanguinetti, Magnus Rattray
Advances in Neural Information Processing Systems, MIT Press 19:785-792, 2007.

Abstract

Modelling the dynamics of transcriptional processes in the cell requires the knowledge of a number of key biological quantities. While some of them are relatively easy to measure, such as mRNA decay rates and mRNA abundance levels, it is still very hard to measure the active concentration levels of the transcription factor proteins that drive the process and the sensitivity of target genes to these concentrations. In this paper we show how these quantities for a given transcription factor can be inferred from gene expression levels of a set of known target genes. We treat the protein concentration as a latent function with a Gaussian Process prior, and include the sensitivities, mRNA decay rates and baseline expression levels as hyperparameters. We apply this procedure to a human leukemia dataset, focusing on the tumour repressor p53 and obtaining results in good accordance with recent biological studies.

Cite this Paper

BibTeX
@InProceedings{Lawrence:transcriptionalGP06, title = {Modelling transcriptional regulation using {G}aussian Processes}, author = {Lawrence, Neil D. and Sanguinetti, Guido and Rattray, Magnus}, booktitle = {Advances in Neural Information Processing Systems}, pages = {785--792}, year = {2007}, editor = {Schölkopf, Bernhard and Platt, John C. and Hofmann, Thomas}, volume = {19}, address = {Cambridge, MA}, publisher = {MIT Press}, pdf = {https://inverseprobability.com/publications/files/gpsim.pdf}, url = {http://inverseprobability.com/publications/lawrence-transcriptionalgp06.html}, abstract = {Modelling the dynamics of transcriptional processes in the cell requires the knowledge of a number of key biological quantities. While some of them are relatively easy to measure, such as mRNA decay rates and mRNA abundance levels, it is still very hard to measure the active concentration levels of the transcription factor proteins that drive the process and the sensitivity of target genes to these concentrations. In this paper we show how these quantities for a given transcription factor can be inferred from gene expression levels of a set of known target genes. We treat the protein concentration as a latent function with a Gaussian Process prior, and include the sensitivities, mRNA decay rates and baseline expression levels as hyperparameters. We apply this procedure to a human leukemia dataset, focusing on the tumour repressor p53 and obtaining results in good accordance with recent biological studies.} }
Endnote
%0 Conference Paper %T Modelling transcriptional regulation using Gaussian Processes %A Neil D. Lawrence %A Guido Sanguinetti %A Magnus Rattray %B Advances in Neural Information Processing Systems %D 2007 %E Bernhard Schölkopf %E John C. Platt %E Thomas Hofmann %F Lawrence:transcriptionalGP06 %I MIT Press %P 785--792 %U http://inverseprobability.com/publications/lawrence-transcriptionalgp06.html %V 19 %X Modelling the dynamics of transcriptional processes in the cell requires the knowledge of a number of key biological quantities. While some of them are relatively easy to measure, such as mRNA decay rates and mRNA abundance levels, it is still very hard to measure the active concentration levels of the transcription factor proteins that drive the process and the sensitivity of target genes to these concentrations. In this paper we show how these quantities for a given transcription factor can be inferred from gene expression levels of a set of known target genes. We treat the protein concentration as a latent function with a Gaussian Process prior, and include the sensitivities, mRNA decay rates and baseline expression levels as hyperparameters. We apply this procedure to a human leukemia dataset, focusing on the tumour repressor p53 and obtaining results in good accordance with recent biological studies.
RIS
TY - CPAPER TI - Modelling transcriptional regulation using Gaussian Processes AU - Neil D. Lawrence AU - Guido Sanguinetti AU - Magnus Rattray BT - Advances in Neural Information Processing Systems DA - 2007/01/01 ED - Bernhard Schölkopf ED - John C. Platt ED - Thomas Hofmann ID - Lawrence:transcriptionalGP06 PB - MIT Press VL - 19 SP - 785 EP - 792 L1 - https://inverseprobability.com/publications/files/gpsim.pdf UR - http://inverseprobability.com/publications/lawrence-transcriptionalgp06.html AB - Modelling the dynamics of transcriptional processes in the cell requires the knowledge of a number of key biological quantities. While some of them are relatively easy to measure, such as mRNA decay rates and mRNA abundance levels, it is still very hard to measure the active concentration levels of the transcription factor proteins that drive the process and the sensitivity of target genes to these concentrations. In this paper we show how these quantities for a given transcription factor can be inferred from gene expression levels of a set of known target genes. We treat the protein concentration as a latent function with a Gaussian Process prior, and include the sensitivities, mRNA decay rates and baseline expression levels as hyperparameters. We apply this procedure to a human leukemia dataset, focusing on the tumour repressor p53 and obtaining results in good accordance with recent biological studies. ER -
APA
Lawrence, N.D., Sanguinetti, G. & Rattray, M.. (2007). Modelling transcriptional regulation using Gaussian Processes. Advances in Neural Information Processing Systems 19:785-792 Available from http://inverseprobability.com/publications/lawrence-transcriptionalgp06.html.

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