Navigation Links
Bioinformatics profiling identifies a new mammalian clock gene
Date:4/22/2014

PHILADELPHIA - Over the last few decades researchers have characterized a set of clock genes that drive daily rhythms of physiology and behavior in all types of species, from flies to humans. Over 15 mammalian clock proteins have been identified, but researchers surmise there are more. A team from the Perelman School of Medicine at the University of Pennsylvania wondered if big-data approaches could find them.

To accelerate clock-gene discovery, the investigators, led by John Hogenesch, PhD, professor of Pharmacology and first author Ron Anafi, MD, PhD, an instructor in the department of Medicine, used a computer-assisted approach to identify and rank candidate clock components. This approach found a new core clock gene, which the team named CHRONO. Their findings appear this week in PLOS Biology.

Hogenesch likens their approach to online profiling of movie suggestions for customers: "Think of Netflix. Based on your personalized movie profile, it predicts what movies you may want to watch in the future based on what you watched in the past." He thought the team could use this approach to identify new clock genes, given criteria already established from the "behavior" of known clock genes identified in the past two decades:

  • Clock genes cause oscillations at the messenger RNA and protein level.
  • Clock proteins physically interact with other clock proteins to form complexes that control daily rhythm inside cells.
  • Disruption of clock genes in cell models cause changes in observable behavioral and metabolic traits on a 24-hour cycle.
  • Clock genes are conserved across 600 million years of evolution from fruitflies to humans.

"We used a simple form of machine learning to integrate biologically relevant, genome-scale data and ranked genes based on their similarity to known clock proteins," explains Hogenesch. Using biological big data such as that found in the Circadian Expression Profile Data Base (CircaDB) to search for new clock genes, the Penn team evaluated the features of 20,000 human genes to isolate other genes that have the same clock-gene characteristics. "The hypothesis is that other genes that functionally resemble known clock genes are more likely to be clock genes themselves, just like movies that resemble your old favorites are more likely to become new favorites," says Anafi.

They found that several of the genes they identified physically interact with known clock proteins and modulate the daily rhythm of cells. One candidate, dubbed Gene Model 129, interacted with BMAL1, a well-known core clock component, and repressed the key driver of molecular rhythms, the BMAL1/CLOCK protein complex that guides the daily transcription of other proteins in a complicated system of genes that switch on and off over the course of the 24-hour day.

Given these results, the team renamed Gene Model 129, CHRONO, for computationally highlighted repressor of the network oscillator. The litmus test for identifying clock genes, however, is whether they regulate behavior: In mice in which CHRONO had been knocked out, Hogenesch found that the mice had a prolonged circadian period.

A companion study by colleagues at RIKEN in Japan and the University of Michigan, using a genome-wide analysis instead of a machine-learning approach, produced similar findings. Both studies link CHRONO to BMAL1. In the future, Anafi and Hogenesch will be investigating whether CHRONO regulates sleep, as most clock genes influence this behavior.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Bioinformatics experts at the CNIO explore additional coding potential hidden in the human genome
2. North America Leads the Largest Market Share of the Bioinformatics Market Says New Research Report by MarketsandMarkets
3. Bioinformatics Market (Molecular Medicine, Agriculture, Research & Forensic) worth $7.5 Billion by 2017 - New Report by MarketsandMarkets
4. Global Bioinformatics Market - Industry Size, Market Share, Trends, Analysis And Forecast 2013 - 2019
5. Global Bioinformatics Market 2014-2018 Industry size, Shares, Research Trends, Growth, Study, Analysis, Forecast
6. First prospective trial shows molecular profiling timely for tailoring therapy
7. North America Leads Cancer Tumor Profiling Market 2018 Forecasts in a New Research Report at RnRMarketResearch.com
8. Cancer/Tumor Profiling Market (Personalized Medicine, Biomarker Discovery, Prognosis, Research) Worth $35.03 Billion by 2018 – New Report by MarketsandMarkets
9. New study identifies promising, achievable solutions to Nigerias childhood mortality crisis
10. Study identifies potential treatment for lethal childhood leukemia
11. New study identifies how information technology is used to solve global health challenges
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Bioinformatics profiling identifies a new mammalian clock gene
(Date:1/19/2017)... ... January 19, 2017 , ... Wells ... facility enhancement of their 503A compounding pharmacy located in Ocala, Florida. , ... physicians and patients throughout the United States for high-quality human anti-aging and ...
(Date:1/19/2017)... ... January 19, 2017 , ... This month, the CEO and ... name of their drug rehab center in Delray Beach, Florida has been changed from ... only stars such as Philip Seymour Hoffman and Chris Farley are dying from heroin ...
(Date:1/19/2017)... , ... January 19, 2017 , ... WhoHaha , ... up with the American Heart Association (AHA) to produce a three-part video series that ... will debut as part of the launch of AHA’s Healthy For Good™ movement, which ...
(Date:1/19/2017)... ... January 19, 2017 , ... Cosmetic Town, an online ... procedures in order to make it easier for their readers to get the information ... they impact as well as the techniques used on those particular areas. , “We ...
(Date:1/19/2017)... , ... January 19, 2017 , ... ... and development solutions for drugs, biologics and consumer health products, today announced that ... with Gattefossé, the leader in innovative excipients and drug delivery solutions to health ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... Calif. , Jan. 19, 2017  Abaxis, Inc. ... manufacturing point-of-care blood analysis instruments and consumables for the ... call to discuss its financial results for the third ... call will be at 4:15 p.m. ET on Thursday, ... for the third quarter fiscal year 2017 after the ...
(Date:1/19/2017)... , Jan. 19, 2017  Sensus Healthcare, ... device company specializing in the treatment of non-melanoma ... keloids, with superficial radiation therapy, today announced that ... year 2016 financial results on Thursday, February 2, 2017 ... will hold a conference call with the investment ...
(Date:1/19/2017)... , January 19, 2017 ... announced that the U.S. Food and Drug Administration (FDA) ... a New Drug Application (NDA) for SHP465, a long-acting, ... as a potential once-daily treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). ... or around June 20, 2017, the designated Prescription Drug ...
Breaking Medicine Technology: