Computational modelling sheds new light on core cell functions

An advanced computational model developed by computer scientists has revealed long delays in gene regulation.

 

The fields of genetics and genomics have developed rapidly during the past years, partly due to better computational methods. Now an international research group led by Finnish researchers has developed a new computational model, which has revealed unexpectedly long processing delays in gene expression following a regulatory signal.

With the help of the new method, measurements of human gene activity made at consecutive time points were analysed. The results revealed that more than 10% of human genes can have delays of more than 20 minutes in their regulation. This is significantly longer than previously thought. The delays were particularly evident in short genes, the activity of which was believed to be fast.

The result will help us to understand life's basic processes in animals and plants and will form a foundation for developing more accurate algorithms to make better sense of gene regulation.

Method inside a method

The researchers studied the response of breast cancer cells to a hormonal regulatory signal that triggers changes in the expression of numerous genes. Some of the genes participate in the response through regulating other genes but these mechanisms are so far poorly understood. More accurate knowledge of gene regulation could enable for example the development of better cancer treatments.

– All gene regulation models are based on assumed effects of regulation, and, if the delay in gene regulation is not taken into account, these can lead to wrong conclusions. The importance of the delays may be compared to a situation where we want to investigate the cause for an allergy when some of the symptoms appear quickly, some only after a long delay. If attention is not paid to this, the investigation will be considerably more difficult and can produce wrong conclusions, Antti Honkela from the University of Helsinki points out.

– We built a physically inspired mathematical model within an advanced statistical model. This made it possible to observe, among other things, the delays of even over 20 minutes that we discovered in gene regulation, tells Jaakko Peltonen from Aalto University and University of Tampere.

New measurement technologies have enabled the investigation of biological phenomena on a vastly greater scale than before. Due to the growth in the scale of data, computational methods are central for all work in the fields of genetics and genomics.

Academy Research Fellows Antti Honkela from the University of Helsinki and Jaakko Peltonen from Aalto University and the University of Tampere were the main authors of the article. They work at the Helsinki Institute for Information Technology HIIT, which is the joint information research unit of Aalto University and the University of Helsinki. They are members of the Finnish Centre of Excellence in Computational Inference COIN appointed by the Academy of Finland. The research was also funded by the European ERASysBio+ ERA-NET programme which is a collaboration of the Academy of Finland and other European science funders as well as the EU.

The article Genome-wide modelling of transcription kinetics reveals patterns of RNA production delays was recently published in the Proceedings of the National Academy of Sciences of the United States of America.

Figure caption: Examples of the observation data and fitted models for different genes. For each gene the upper red curve depicts its transcriptional activity and the lower green curve the expression of mature messenger RNA. The distribution of the delays estimated between these is shown on the right.

 

Created date

12.10.2015 - 14:16

Brain poetry

In the latest research result of the month section, we interview PhD student Jukka Toivanen about his recent work on brain poetry in the Discovery group led by professor Hannu Toivonen. How can humans and machines be creative together?

Kjell Lemström to be new Head of Studies

Since Jaakko Kurhila left the department to head the Open University, we had to find a new university lecturer to act as head of studies in short order. We received a total of 28 applications. Out of these, and after a preliminary qualification round, evaluations, interviews, and a department council hearing, Kjell Lemström (KL) was elected for the post. He started working as the department's Head of Studies on 2 March 2015, so the Head of the department (JP) conducted the following induction interview that very week.

This is by no means the first time Kjell has been employed by the department. He defended his thesis on ‘String Matching Techniques for Music Retrieval’ in 2000, and has held numerous teaching and research positions both before and after that, until he transferred to the Laurea University of Applied Sciences in 2011 (luckily, that was only temporary).

Head of Studies Jaakko Kurhila to head Open University

The Head of Studies at the department, University Lecturer Jaakko Kurhila, has been elected to the post of director of the Open University at the University of Helsinki. It was a tough race: all in all, 39 applicants sought the post, some of them through the Mercuri Urval headhunting process. After a consultant evaluation, interviews, and aptitude assessments, the preparatory committee for the post, the steering committee for the Open University, and the rector of the university came to a unanimous decision to select Jaakko, and the contract is already being drawn up.

Being selected from this prestigious group of applicants, and after such a thorough process, is indisputable proof of the qualifications of Jaakko and the high esteem the academic community has for him. The department extends its warmest congratulations to Jaakko for this career development and is proud of the success of its protégé.

Bridging the Gap Between Research and Standardization

In the fourth research result of the month, we report a joint work between the UH NODES group and the Cambridge NetOS group, lead by Prof. Sasu Tarkoma and Prof. Jon Crowcroft, respectively. Their work recently received the best paper award "Best of CCR" from ACM SIGCOMM.