Phew... now Systems Biology is everywhere!

Gone are the days when people kept on rolling new names through the books' release. You coin the term, blog it and blow it. Today, systems biology is eyeing everywhere. Akin to many, systems biology to me is not just deciphering biology of a system, protein-protein interactions, fluxes, metabolism but a deep-rooted biology within an organism, finally providing us the clues in the form of a "functome". I peg my thoughts on the challenges this multi-dimensional biology has brought in annotation of proteins especially annotating the un-annotated.

Start 2006, whence my PhD studies were middle way, I wondered what and how systems biology could teach me about hypothetical proteins in human. The then draft release of human genome came across several hypothetical proteins. The ensuing drafts too provided no significant clues and had no or little change in the numbers. The obvious reason was that these proteins are electronically annotated. Does electronic annotation mean an elegant footnote? Is it unswerving? Does manual annotation follows electronic annotation? Does it bring any change in number of hypothetical proteins or proteins awaiting function? There were more questions than answers. The top-down systems biology delve upon how we could make use of umpteen proteins and study interactions while the bottom-up systems biology explore the metabolic fluxes, pathways and ins and outs towards the function of the genes (figure 1).

Figure 1

About Our Guest Blogger:

Prash works at Bioinformatics team, CDAC, Pune, India. He also serve as an Associate Director of Bioinformatics.org. He founded Bioclues.org in 2006, a virtual organization, that masks projects online and builds mentor-mentee relationship.

"Plastics" may have been the Baby Boomer watchword, but "synthetic" rules today

via usatoday.com

Human Pharmacometabonomic: Researchers identify a clear connection between an individual's metabolic phenotype and metabolic fate of a standard dose

Pharmacometabonomics is a novel approach that utilizes metabolic phenotypes to predict the drug metabolism or xenobiotic toxicity. In recent a recent article in journal PNAS T. Andrew Clayton et al. demonstrate a pharmacometabonomic approach in humans. It is important to note that previously pharmacometabonomics has been demonstrated in rats. Study reports a clear and significant association between metabolic fate, liver damage, and predose metabotype.

We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by ¹H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.

This study is important because it provides

a convincing demonstration of pharmacometabonomics in humans while at the same time revealing a hitherto-unrecognized specific effect of the gut bacteria on drug sulfation and detoxification. This work may well have important implications for individual patients via the improved delivery of personalized medicine studies, thus influencing the policies of healthcare providers and drug discovery and development.