A Mathematical Model for Enhancer Activation Kinetics During Cell Differentiation

Kari Nousiainen*, Jukka Intosalmi, Harri Lähdesmäki

*Tämän työn vastaava kirjoittaja

Tutkimustuotos: Artikkeli kirjassa/konferenssijulkaisussaConference contributionScientificvertaisarvioitu

Abstrakti

Cell differentiation and development are for a great part steered by cell type specific enhancers. Transcription factor (TF) binding to an enhancer together with DNA looping result in transcription initiation. In addition to binding motifs for TFs, enhancer regions typically contain specific histone modifications. This information has been used to detect enhancer regions and classify them into different subgroups. However, it is poorly understood how TF binding and histone modifications are causally connected and what kind of molecular dynamics steer the activation process. Contrary to previous studies, we do not treat the activation events as static epigenetic marks but consider the enhancer activation as a dynamic process. We develop a mathematical model to describe the dynamic mechanisms between TF binding and histone modifications known to characterize an active enhancer. We estimate model parameters from time-course data and infer the causal relationships between TF binding and different histone modifications. We benchmark the performance of this framework using simulated data and survey the ability of our method to identify the correct model structures for a variety of system dynamics, noise levels and the number of measurement time points.

AlkuperäiskieliEnglanti
OtsikkoAlgorithms for Computational Biology - 6th International Conference, AlCoB 2019, Proceedings
ToimittajatMiguel A. Vega-Rodríguez, Ian Holmes, Carlos Martín-Vide
Sivut191-202
Sivumäärä12
DOI - pysyväislinkit
TilaJulkaistu - 1 tammikuuta 2019
OKM-julkaisutyyppiA4 Artikkeli konferenssijulkaisuussa
TapahtumaInternational Conference on Algorithms for Computational Biology - Berkeley, Yhdysvallat
Kesto: 28 toukokuuta 201930 toukokuuta 2019
Konferenssinumero: 6

Julkaisusarja

NimiLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
KustantajaSpringer
Vuosikerta11488 LNBI
ISSN (painettu)0302-9743
ISSN (elektroninen)1611-3349

Conference

ConferenceInternational Conference on Algorithms for Computational Biology
LyhennettäAlCoB
MaaYhdysvallat
KaupunkiBerkeley
Ajanjakso28/05/201930/05/2019

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  • Siteeraa tätä

    Nousiainen, K., Intosalmi, J., & Lähdesmäki, H. (2019). A Mathematical Model for Enhancer Activation Kinetics During Cell Differentiation. teoksessa M. A. Vega-Rodríguez, I. Holmes, & C. Martín-Vide (Toimittajat), Algorithms for Computational Biology - 6th International Conference, AlCoB 2019, Proceedings (Sivut 191-202). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vuosikerta 11488 LNBI). https://doi.org/10.1007/978-3-030-18174-1_14