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:6/25/2016)... ... 25, 2016 , ... Experts from the American Institutes for ... Meeting June 26-28, 2016, at the Hynes Convention Center in Boston. , AIR ... care planning, healthcare costs and patient and family engagement. , AIR researchers will ...
(Date:6/25/2016)... ... , ... First Choice Emergency Room , the largest network of independent ... Director of its new Mesquite-Samuell Farm facility. , “We are pleased to announce ... Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , ...
(Date:6/25/2016)... Canada (PRWEB) , ... June 25, 2016 , ... Conventional ... pursuit of success. In terms of the latter, setting the bar too high can ... risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... ... ... Marcy was in a crisis. Her son James, eight, was out of control. Prone to ... , “When something upset him, he couldn’t control his emotions,” remembers Marcy. “If there ... my other children and say he was going to kill them. If we were ...
(Date:6/24/2016)... ... 2016 , ... Comfort Keepers® of San Diego, CA is excited to announce ... program to drive cancer patients to and from their cancer treatments. Comfort Keepers ... of life and ongoing independence. Getting to and from medical treatments is one ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... June 27, 2016  VMS Rehab Systems, Inc. ( ... take whatever measures required to build a strong and ... is currently listed on the OTC Markets-pink current trading ... and CEO, "We are seeing an anomaly in market ... not only by the Company, but shareholders and market ...
(Date:6/24/2016)... , June 24, 2016  Global Blood Therapeutics, ... company developing novel therapeutics for the treatment of ... announced the closing of its previously announced underwritten ... at the public offering price of $18.75 per ... were offered by GBT. GBT estimates net proceeds ...
(Date:6/24/2016)... The Academy of Managed Care Pharmacy (AMCP) ... would allow biopharmaceutical companies to more easily share health ... and coverage decisions, a move that addresses the growing ... The recommendations address restrictions in the sharing of ... label, a prohibition that hinders decision makers from accessing ...
Breaking Medicine Technology: