Next-generation genome sequencing

By Catherine

Written by Catherine Bolgar

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“Next-generation sequencing” (NGS) is the latest step in genomic sequencing. Currently NGS is used mostly in the lab, but possibilities for clinical applications are opening up.

Sequencing of the entire human genome was completed in 2003, a process that took over a decade. The goal was to identify all the three billion base pairs of deoxyribonucleic acid (DNA) in our 23 pairs of chromosomes. Genes are segments of the chemical compound DNA, passed down from parents to children, and mutations in our genes are linked to many diseases, from cancer to inherited conditions such as sickle-cell disease, cystic fibrosis or Tay-Sachs disease.

Faster computers, new technology and better optics are giving medical researchers a big boost, while also cutting costs. For example, the supercomputer at the Argonne National Laboratory near Chicago— jointly ordered by Argonne and the University of Chicago in 2010—can analyze 240 whole genomes simultaneously in two days, compared with the several months it takes to analyze a single whole genome with less extraordinary computers.

The speed and depth of coverage for looking for mutations has improved,” says Glen J. Weiss, director of clinical research and medical oncologist at Cancer Treatment Centers of America at Western Regional Medical Center in Goodyear, Arizona, and associate professor in the cancer and cell biology division at the Translational Genomics Research Institute (TGen), based in Phoenix.

“Turnaround time for getting results has improved. Is it ready for direct clinical applications? At this time, yes, though in a fairly limited way.”

Many of the genes being sequenced don’t yet have a sufficiently complete picture to apply to clinical use. “Whole-genome sequencing is still research-oriented, trying to identify mutations associated with carcinogenesis,” Dr. Weiss says.

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Research isn’t restricted to DNA. Ribonucleic acid (RNA) also plays a role in cells, passing genetic information from DNA to proteins. New aspects of RNA’s importance have only recently been uncovered. The set of all RNA molecules is called the transcriptome. Exons are the part of the gene that encodes proteins, and all the exons in a genome are called the exome.

NGS comprises whole-genome sequencing, selected gene-set sequencing, whole-exome sequencing and whole-transcriptome sequencing, as well as other techniques, such as massively parallel sequencing.

Whole-exome sequencing is mostly used in research, for example to find genes related to glaucoma. In the clinic it has helped doctors pinpoint previously undiagnosed uncommon genetic diseases in patients.

Whole-genome sequencing has been used on cancer patients to compare tumor DNA with patients’ normal DNA, so doctors can choose the best treatment based on the mutations that were found. Treatments are specific to the cancer’s genetic profile, so speedy analysis of that profile is essential for patients with metastatic cancer.

Whole-genome sequencing also has been used on pathogens, such as bacteria. Real-time sequencing of Acinetobacter baumannii, a bacterium which is resistant to many drugs and which attacks severely ill patients, helped Queen Elizabeth Hospital Birmingham in the U.K. control an outbreak of a new strain of A. baumannii. Similarly, it was used to track methicillin-resistant Staphylococcus aureus (MRSA) in other hospitals in the U.K. and Thailand.

Whole-transcriptome sequencing has found genetic markers in blood related to post-traumatic stress disorder, uncovered a cellsignaling pathway related to inflammatory bone erosion and rheumatoid arthritis, as well as revealing which genes are active in human muscles and how muscles in men and women differ.

Dr. Weiss was part of a team using a combination of whole-genome sequencing and whole-transcriptome sequencing to identify more targets in a person’s tumor—targets that might respond to specific treatment.

However, “for the most part, in the past 15 years, using precision medicine and sequencing based on tumors has not yielded as much success as we would have liked,” Dr. Weiss says. When imatinib hit the market in 2001 as a treatment for chronic myeloid leukemia (CML), a cancer of the white blood cells, “we thought targeting would be the cure-all for all cancers. The naivety of researchers, then, is that CML has only one driver abnormality,” he says. “But other cancers can have a whole slew of other abnormalities, instead of just one, but dozens of molecular subtypes.”

cancer cellFor example, several years ago lung cancer was linked to only a couple of genetic mutations. Today, we know that “there are about 15 different mutations, and each has a unique prognosis and outcome with a drug,” Dr. Weiss says. However, “if you look at a pie chart of how much individual mutation makes up out of the overall lung-cancer population, for nearly half of cases we don’t know what’s driving the cancer,” he adds “There are still a lot of unknowns.” What we do know for sure is that genetic sequencing has a growing role to play in medical research.

 

Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion.

 

Photos courtesy of iStock

Industrializing Construction: Solutions for Productivity Breakthroughs

By Akio

This post is an excerpt from the paper, “Industrialization of the Construction Industry,” by Dr. Perry Daneshgari and  Dr. Heather Moore of  MCA Inc.

An important study by the National Research Council, Advancing the Competitiveness and Efficiency of the U.S. Construction Industry” identified solutions for breakthrough improvement of productivity.

Five Key Areas for Productivity Improvements in Construction

  1. Widespread deployment and use of interoperable technology applications.
  2. Improved job-site efficiency through a more effective interface of people, processes, materials, equipment, and information.
  3. Greater use of pre-fabrication, pre-assembly, modularization, and off-site fabrication techniques and processes.
  4. Innovative, widespread use of demonstration installations.
  5. Improved performance measurement to drive efficiency and support innovation.

Tweet: Do you know the 5 Key Areas for Productivity Improvements in Construction? @3DSAEC @Dassault3DS #AEC http://ctt.ec/02ELV+Click to tweet: “Do you know the 5 Key Areas for
Productivity Improvements in #Construction?”

These findings are very much in line with what the manufacturing industry had realized after the advent of industrialization. The Industrial revolution, which started in mid 1700, led to an increase in population due to the first time in the human history that production levels were higher than self-consumption of the working man.

Timeline of Industrialization

 

With higher population also came new markets and customers. The production facilities had to become more productive.

Henry Towne introduced the concept of “Engineer as an Economist,” and led the path to the application of “Principles of Scientific Management” by Fredrick Taylor for discovering the means of managing labor and work.

Continuing with giants of productivity improvements such as Frank and Lillian Gilbreth for efficiency, human factors, and measurement; Henry Ford for efficiency of the machine; Dr. Shewhart and Deming for statistical process control; and ending with Toyota’s Taichii Ohno for application of effectiveness of labor, the manufacturing gained its four to five-fold productivity.

Toyota assembly line

This post is an excerpt from the white paper, “Industrialization of the Construction Industry,” by Dr. Perry Daneshgari and Dr. Heather Moore.

Commissioned by Dassault Systemes and prepared by MCA Inc., this whitepaper focuses on industrialization of construction industry.

It maps out the construction industry challenges, relates the history of industrialization in the manufacturing industry, and summarizes five critical aspects and approaches.

Download the whitepaper and start accelerating the “Industrialization of the Construction Industry” through lessons learned from manufacturing and other industries.

Tweet: Industrializing #Construction: Solutions for Productivity Breakthroughs @3DSAEC @Dassault3DS #AEC #BIM http://ctt.ec/BfR96+

Click to tweet this article

Akio Moriwaki

Akio Moriwaki
Dassault Systèmes’ head of global marketing for the Architecture, Engineering and Construction industry, Mr. Moriwaki led the launch of the groundbreaking Lean Construction Solution Experience and is a member of buildingSMART.

Related resources:

Optimized Construction Industry Solution Experience

Download Optimized Construction Solution Brief

White Paper: Industrialization of the Construction Industry

MCA® Website

Water, Water, Leaking Everywhere

By Catherine

Written by Catherine Bolgar

courtesy: iStock

A quarter or more of the world’s expensively treated drinking water never reaches a faucet as a result of aging, leaky infrastructure. Around 14% of treated water in the U.S. is lost, with some cities losing as much as 60%. Water leaks cost Europe around €80 billion a yearCroatia, for example, wastes almost 40% of its water.

Fritz Barth, vice chairman of the European Water Partnership (EWP), notes: “We have a lot of old infrastructure with a lot of leakage. Clean drinking water is prepared, and then a lot of it just leaks into the ground. It’s a big waste of energy, effort and water.”

Water companies do respond when a water main breaks (which occurs on average 850 times a day in North America). But less dramatic leaks are not fixed, either because they go undetected or because of the high repair cost.

“Water is too cheap,” Mr. Barth says. “The price often covers only the service of delivery to the home. It doesn’t cover the replacement of old infrastructure. Utilities can’t put aside money for reinvestment.”

The problem is not just with our drinking water. Sewage pipes are also aging and leaking. “If you have leaking wastewater pipes and leaking drinking-water pipes, it’s even worse,” Mr. Barth says. “The drinking-water pipes can suck in the wastewater.”

courtesy: iStockMoreover, some 80% of the world’s wastewater flows untreated into rivers, lakes and oceans. The difficulties are compounded as developing-world cities expand faster than they can install infrastructure.

More effective recycling would help. Densely populated Singapore, which imports one-third of its water from neighboring Malaysia, operates a water-recycling program called NEWater. Recycled water now meets 30% of the country’s water demand—particularly from its semiconductor plants—and this figure is expected to increase to 55% by 2060. NEWater also contributes to reservoirs during dry periods, where the water is further treated to become drinkable.

Many people may recoil from the idea of “toilet-to-tap” water recycling, but they are already doing it, Mr. Barth points out. Upstream cities dump treated wastewater into rivers that supply drinking water to utilities downstream. Recycling could happen in individual buildings. Rather than pumping sewage and drinking water to and from centralized treatment plants, new technology allows for decentralized water treatment.

A recycling system the size of a household washing machine can also treat water used in apartments or office buildings. The system removes the “raw materials” and uses the remaining gray water to irrigate gardens or, more importantly, flush toilets—which account for 27% of total indoor water use in the U.S.

However, many municipalities still prohibit the use of gray water, including harvested rainwater, even for toilet flushing or irrigation. “Wastewater and drinking-water legislation is quite old,” Mr. Barth says, and needs to be updated in light of new technology and society’s needs.

courtesy: iStockManufacturers have improved indoor technology since “low-flow” showerheads and toilets were introduced. Producers are now focusing on getting the same or better results with less water. For example, by infusing air between water droplets, a shower can be just as forceful with less water, says Barbara C. Higgens, chief executive officer of Plumbing Manufacturers International.

WaterSense toilets, showerheads and faucets, developed since 2006, could save drought-stricken Californians 360 million gallons of water a day, Ms. Higgens says.

“People will stand in line for the latest phone, but when it comes to water-efficient technology most are using toilets, showers and faucets made more than 20 years ago.”

Reducing water flow rates can, however, have unintended consequences. In Germany, for example, drastically lower water usage has forced some municipalities to flush their sewer pipes. One solution might be to replace leaky, sometimes 100-year-old, systems with new, smaller pipes. As EWP’s Mr. Barth points out, one wouldn’t even need to dig trenches: smaller pipes could be threaded through the old ones, while sensors could be installed to detect leaks and send alerts.

 

Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion.

 

Photos courtesy of iStock



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