Archive by category | Computational approaches

Top-down mapping of gene regulatory pathways

Top-down mapping of gene regulatory pathways

In a very recent lecture (see full video from NIH VideoCasting) given for the NIH Systems Biology Special Interest Group, Trey Ideker presents a great overview of the various strategies his group has been developing in the recent years in order to integrate multiple types of large scale datasets. While one of the most pervasive ‘meme’ about high-throughput measurement is that they are “notoriously unreliable” (see Hakes et al, 2008, for a recent example), Trey beautifully illustrates how predictive computational models and novel biological insights can be generated by sophisticated data integration strategies. Three types of applications are presented in his talk:  … Read more

Transcription paused and poised for regulation

Transcription paused and poised for regulation

Research highlight by Frank C.P. Holstege, Department of Physiological Chemistry, University Medical Center Utrecht, the Netherlands. For eukaryotes, it is widely thought that transcription is primarily regulated through recruitment of the essential machinery to transcription start-sites. Previous hints challenging this paradigm have been confirmed by recent analyses showing that transcription regulation of a large number of genes actually occurs after recruitment. Mechanistically, such studies have gone furthest in Drosophila melanogaster (Muse et al, 2007; Zeitlinger et al, 2007). Here, conservative estimates indicate that more than 10% of genes are regulated through promoter-proximal pausing. On such genes, RNA polymerase II is  … Read more

Morphogen Paradoxes

Morphogen Paradoxes

A controversy seems to be brewing over some recent theories and quantitative analyses addressing the fundamental question of how the Bicoid morphogen gradient is established and decoded in early Drosophila embryos. The transcription factor Bicoid controls the anterior-posterior patterning of the developing embryo. It is translated from maternal mRNA localized at the anterior pole of the egg and its graded distribution activates, in a concentration-dependent manner, the expression of gap genes, thus determining their spatial domain of expression. Synthesis from a localized source combined with diffusion and uniform degradation of the Bicoid morphogen provides one of the simplest models to explain the approximately exponential shape of its gradient.  Read more

Consumer Health Information Technology

Consumer Health Information Technology

I highly recommend to visit the NIH VideoCasting page, which hosts many interesting video/podcasts. Even if I realize that this is a bit old according to the blogosphere time scale, I would like to point to this one: “The Future: Consumer Health Information Technology”, featuring talks given at a NCI-sponsored meeting on Dec 10, 2007 by Adam Bosworth (formerly “Google Health architect”, now starting his own company Keas), Bern Shen (Intel) and Bill Crounse (Microsoft). In his introduction to the meeting, Bradford Hesse (NCI) colorfully summarizes one of the main concepts exposed by the speakers (the video is very long,  … Read more

Personal genomics for a fistful of dollars

Personal genomics for a fistful of dollars

The wave of personal genomics is progressing rapidly. A string of four papers appeared recently (Porreca et al, 2007, Albert et al, 2007, Okou et al 2007, Hodges et al, 2007) reporting on microarrray-based technologies that enable the enrichment of selected genomic fragments in a single massively multiplexed reaction, thus greatly facilitating subsequent resequencing of pre-defined portions of the human genome (eg all coding exons). These technologies are expected to reduce dramatically the cost of targeted resequencing of individual genomes.  Read more

Glia-neuron interactions

Glia-neuron interactions

Nature Neuroscience has a nice special focus on glia and disease. The featured reviews and perspective articles discuss multiple aspects of neuron-glia interactions and their role in disease. The reason why I am highlighting this collection here is that I have the feeling that this field could potentially be a nice playground for systems biology. For example, Rossi and colleagues (2007) review the various metabolic processes affected during brain ischemia. Several of the examples discussed illustrate very well how the extent of brain damage is determined by the concurrent dynamics of both harmful and protective processes engaging complex interactions between  … Read more