Science: GWAS = genome wide association study

As a molecular biologist/biochemist trained in the 20th century, I have to say my head is on a swivel trying to keep up with all the new technology being used in research.

Old school molecular biology and biochemistry techniques are being pushed to new levels made possible by the nanotechnology and computer revolutions. One such implementation is the GWAS, genome wide association study.

The idea is based on the fact that there are genetic variations in the human population. Thus, population X (without disease condition Y) is compared against population Z (with disease condition Y). Do the genetic variants distribute the same in population X and population Z?

For example, let's say there is a gene variant P that exits in 75% of the study population (X + Z). If P is NOT associated with disease condition Y then P should show up in population X and Z at 75%. But, in an extreme example, variant P shows up in 55% of population X and 95% of population Z then you would say variant P is associated with disease Y.


Of course, that is an extreme example and real life the data is much less clear cut. And of course, correlation (or association) is not causation.

Came across this article with the provocative title, Have We Wasted 7 Years and $100 Million Dollars on GWAS Studies?

The author rightly points out the technical challenges of conducting such experiments and the limits of the interpretation of the data. And certainly, it looked bleak for whether it has been worthwhile. But in the end, he concludes, that is science, you got to try and see what happens and that these efforts lay a foundation for future experiments. He summarizes:

So has it been worth it to spend over $100 million dollars in research funding on these studies over the past seven years?

Yes.

But not because we discovered lots of actionable genetic markers. We haven’t.

And not because we have achieved a genetic understanding of common (and costly) diseases as we promised in our grants. We haven’t.

But science isn’t about delivering on a business plan.

Science is about discovery; breaking ground on venues of research that were previously entirely uncharted or unknown.

Already, follow-up studies are taking a deeper look at the genomic regions associated with certain traits.

Some of these studies are looking to close the gap of missing heritability by using Next-Generation Sequencing and new hypothesis about the biological architecture of common and chronic diseases.

With the expectation that genetics will play a large role in how clinical practice of medicine approaches preventative and personal care, there is an enormous amount of research left to make an individual’s genome actionable.

I’ll be watching closely.

News: Medal of Honor to Clint Romesha

The incredible story of the battle at COP Keating and the role of Clint Romesha had on that day by Jake Tapper.

The base was attacked from all sides by Taliban early in the morning and nearly overrun. Romesha and his team was able to fight back.

An amazing story of courage under fire.

Valor according to Merriam Webster:
strength of mind or spirit that enables a person to encounter danger with firmness : personal bravery

Of course, Romesha, as have other recent recipients of the Medal of Honor have said, they simply did what they had to do.  Romesha said after the ceremony:
"I stand here with mixed emotions of both joy and sadness for me today," he said. "I don't think I'm much different than Medal of Honor recipients Sergeant First Class Petry and former Staff Sergeant Giunta and feeling conflicted with this medal I now wear. But joy comes from recognition for us doing our jobs as soldiers on distant battlefields, but is countered by the constant reminder of the loss of our battle buddies, my battle buddies, my soldiers, my friends." Romesha said he accepted "this tremendous honor on behalf of all soldiers who have served with me that day." "This award is for the eight soldiers that didn't make it and for the rest of the team that fought valiantly and magnificently that day. I will forever be humbled by their bravery, their commitment to service and their loyalty to one another."

Theology: What does Psalm 110:5 mean?

"The Lord is at your right hand; he will crush kings on the day of his wrath." Psalm 110:5 (TNIV)

I've seen three interpretations of this verse:
(1) The Lord God is at Messiah's right hand; God will crush kings on the day of his wrath.
(2) Lord God, at your right hand is Messiah who will crush kings on the day of his wrath.
(3) Messiah is at God's right hand; Messiah will crush kings on the day of his wrath.

For the kings who get crushed on the day of wrath, it doesn't really matter which of the three is the correct interpretation!

Nonetheless, which interpretation is most likely to be correct and why?

Are there some other interpretive options to consider?

In memoriam: Kuan-Teh Jeang, 1958-2013

Earlier this week, I was working on slides for our departmental research seminar where I would present results from our collaborative research project we have with a clinical group at the Children's Hospital of Philadelphia. The talk was informatively if dryly titled, "Immunomodulatory Effects of Vitamin D3 Supplementation in Children, Adolescents and Young Adults with HIV/AIDS." As I prepared, emails starting arriving in my inbox from all over the world with news of the sad and sudden death of Kuan-Teh Jeang. I decided to include some brief remarks at the beginning of the seminar. I hope in some small way these thoughts could honor Teh's memory and encourage the young researchers in the audience. Text of what I shared this morning are below.

Before I start today’s seminar, I would like to offer some brief remarks in memory of Kuan-Teh Jeang who died last Sunday, January 27 at age 54. I was a post-doctoral fellow in his lab at the NIH from 1993 to 1997 working on the molecular biology of HIV.

This photograph (shown above) is from 2012 when he gave the George Khoury lecture in October. This named lecture was started at the NIH in 1994 to recognize the highest levels of scientific research and to remember Dr. Khoury who was one of the bright stars of the NIH who died much too soon. It should be noted that Teh started his scientific career as a post-doctoral fellow in George Khoury’s lab about 25 years ago. And so giving the lecture was both a tremendous scientific and personal occasion for Teh. Who could have known that three months later another one of NIH’s leading lights would pass away much too soon. Suffice to say, Teh’s scientific accomplishments in the field of the molecular biology of human retroviruses were numerous and are best detailed in official remembrances of his life.

I’ll simply say, it was a tremendous honor to work at the NIH for those four years. Teh was the energetic and tireless leader of our research group dedicated to peeling back what was unknown about HTLV and HIV. On a personal level, since our group was composed of post-docs who came from far and wide from Washington DC, he generously gave personal attention and practical help to us, his incoming post-docs. Those simple kindnesses helped us settle into our lives in and around Bethesda.

May God rest his soul and comfort his wife and three children who remain.

Remarks by Michael Gottesman at Retrovirology.
Post at BioMedCentral.
Comment from Journal of the International AIDS Society.
Statement at Cell and Bioscience.
Notice at the NIAID/NIH web site.

As part of the network of lab alumni, I've received notice that two longer recollections will be published at Cell and Bioscience and Journal of Biomedical Sciences. I will link to them when they go live.

UPDATES:
Obituary at Journal of Biomedical Sciences.
In memoriam at Cell and Bioscience.
Editorial item at Cell and Bioscience.