Author and Reporter: Anamika Sarkar, Ph.D
Early in the month of September, Nature, published 30 research papers on the results found from the ambitious and one time felt risky project, named, ENCODE (Encyclopedia of DNA Elements). The results of ENCODE revealed that 80% of human genome is not “junk”, as thought before, rather act as regulatory domains for further signaling events.
When human genome was first sequenced, more than a decade ago, scientists were surprised with the low ratio of coding regions transcribing genes to the number of bases in human DNA. Out of 3 billion bases in human DNA scientists found only 21,000 genes. This unexpected finding led to few basic questions:
- Why do humans have so many base pairs?
- How highly regulated complex behaviors of biochemical, cellular and physiological processes can be translated to regulation at genetic levels?
ENCODE project results unveil our limited knowledge about human genome until now. Their results open up new ways of thinking human DNA and its functional domains. It also brings in huge challenges for both experimental developments and data driven computational approaches for better understanding and applications of these new findings.
To gain insight from large scale data and identifying key players from a large pool of data, Bioinformatics approaches will probably be the only way to move forward. This also means importance of developing new algorithms which will include the capability of including regulatory functions linking with gene regulation. Presently, most algorithms are targeted toward identifying genes and their connections in a linear fashion. However, regulatory domains and their functional activities might be non linear, something which will be revealed with many more experimental results in coming years.
The functional characteristics of human genome will also lead to better understanding of genetic differences between normal states and disease states. Moreover, with proper identification of functional characteristics of a particular gene regulation, drugs can be targeted with much more precision in future. However, to make success of such a complicated problem, it will require visionary design and execution of experiment and computational biology teams working together.
It is well recognized already that Bioinformatics approaches can hugely help in identifying key players in regulation of genes. However many times it is not easy to translate information at the genetic levels directly to cellular or physiological levels. Some of the main reasons are – a) the complex cross talks between proteins which lead to intracellular signaling events and b) highly non linear information sharing among receptors and ligands for extra cellular signaling processes. To achieve efficient understanding of the functional characteristics of non-coding regions of DNA in context with regulation of genes, an effort should be given to map the functional network of gene regulation to signaling pathways of protein networks. This will require development of experimental as well as computational approaches to capture genetic as well as proteomics analysis together. Furthermore, for better understanding of cellular and physiological decisions, mapping between regulations of genes and intracellular signaling pathways should be extended for dynamic analysis with time.
The extraordinary findings from ENCODE project pose many challenges in front for getting answers to many unknowns for next decade or so but also give solutions to some basic questions which have haunted scientific world for almost a decade.
Sources:
News and Views- ENCODE explained: http://www.nature.com/nature/journal/v489/n7414/full/489052a.html
News and Analysis – ENCODE Project writes Eulogy for Junk DNA : http://www.sciencemag.org/content/337/6099/1159.summary?sid=835cf304-a61f-45d5-8d77-ad44b454e448
ENCODE Project (Nature Article): http://www.nature.com/nature/journal/v489/n7414/full/nature11247.html
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Anamika,
Thank you for your post.
I will read and comment during the day.
Please connect to Your Groups on LinkedIn twitter and facebook
This is fabulous. I am quite certain that these processes are not linear, but it is simpler for us to view them that way. The Watson-Crick model has a linear arrangement of base pairs. But now there is serious reason to expand the alphabet, and there are synthetic nucleotides/nucleoside that van pair with a hydrophobic (not hydrogen bonding) attachment. We also don’t understand the d-orbital in key analytes allowing for multiple intermediates from several valence states. The handling of nonparametric algorithms has come far. Proteomis is the first step toward reaching the metabolic phase.
I like that comment.
Thank you Dr. Larry for your validation of my thought. I am trained to see our human body as the best machine with least redundant activities. Thus, non linearity is absolutely required to make the processes efficient. However, starting with linear processes has always led scientists to know more about the system, and then adding non linearity slowly allows scientists to know furthermore about the system. Else, it can become out of control very fast. I agree with you I do think there will be need for expanding the alphabets.Moreover, I think one should be careful to identify the degree of importance in regulatory functional activities as the set of alphabets increase.
Anamika,
This is a daring critical thinking evaluation of the the three sources with your own expression as of what the state of affairs are, may be in the future and WHAT is mostly needed to achieve progress. Thus, your post exemplify the excellence of your own thought process and a great ability to articulate it to the reader. Both as necessary and sufficient in most case to be positioned for planning the next breakthrough.
I would consider to suggest to you for your consideration to change the title of the post along the lines of:
The Unknown yet about Junk DNA: Mapping the functional network of gene regulation to signaling pathways of protein networks.
If you change the title, please reconnect to all your Groups.
Thank you for a great evaluation of the state of Affairs related to ENCODE.
Thanks Aviva for your comment. I think my article is a cautious warning to the future.
A decade ago, during the invent of human genome sequence and micro array technology and Bioinformatic algorithms, we (scientific world) missed the point that gene is the smallest machinery of cellular and physiological processes. It took another half a decade to identify the importance of new experimental techniques at protein or physiological levels.
Computational models need both inputs and validations to be able to successfully predict either dynamic processes or specific targets. Thus, I wanted to make a cautious point of view to bring attention to the state of art findings from ENCODE which can be used in much more efficient manner with collaborative efforts of different fields together and help us to identify better drug targets and better healthy life.
I see your point that the title might not be reflection of my point of view of the article. Hence, I am changing it to reflect more the content in the article.
Great I am posting it on my Groups with the new Title.
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Its just been my primary steps towards research in this avenue, and I find more than the need of churning out data, its important to analyse them. What a contribution,I really thank you for these efforts. Each time we have anything sequenced its like ancient hieroglyphic code, and understanding it opens up new doors to research.However my naive thoughts say that 80% of genetic content, not everything can be junk there will be some hidden treasure somewhere we (As you say scientific world) are on a hunt.