Future Opportunities for Genome Sequencing and Beyond

March 2, 2015

Workshop Report


Some quoted snippets that people felt were interesting:


NHGRI has been a leader in creating ontologies and standards, and should continue to lead in this area. Given the large amount of sequencing occurring in the world, NHGRI could undertake steps to catalog different sequencing efforts, and to ensure that data are shared in truly useful ways. Given that raw data cannot always be shared, it is also important to improve interoperability and collaboration. Through these types of efforts the collective sequence data become a much more powerful resource for everyone.

The goal of identifying the mutations underlying all Mendelian conditions – the great majority of which are loss-of-function – is the human equivalent of the mouse knockout project, and is of great importance to understanding of both human biology and genomic medicine.

As discussed in the NHGRI Strategic Plan, continued acquisition of knowledge on genome function is valuable for understanding the biology of genomes and the genomic basis of disease. Integrating variant discovery with analysis of genome function can help with prediction of the following: causal variants based on identified tag variants; target genes and cell types based on disease associations; and mechanisms by which pathogenic variants act.

A paradox of precision medicine is that sequencing data needs to be generated in large numbers of subjects to interpret what is seen in individual patients.

Sequencing and alignment of primate and vertebrate genomes has led to identification of >3 million evolutionarily conserved elements and improved understanding of the origin of human and mammalian lineages. …
The amount of exome and genome data generated in research and clinical settings is expected to continue to increase significantly. NHGRI cannot expect to be a primary driver of sequence production and capacity. However, the Institute can take a catalytic lead in setting standards, improving and implementing new test methods, disseminating and integrating information, and serving as a model for other groups. A suggestion is for NHGRI to fund multiple pilot activities to explore how to organize capabilities and resources.

Consideration should be given to implementing foundational resources that make sequencing broadly useful for discovery and clinical applications. NHGRI needs to enhance public awareness of the process, progress and success of our programs. As one example, projects “building” for the future should be complemented by projects that can have fruitful products on a shorter timescale. Demonstrating impact and showing objective measures of progress are needed to maintain support of the rest of the community.

Functional Genomics

Large-scale centers with generalized capacity for assessing variant function are likely premature, because the most universally valuable data types and methods to take to scale are not yet known. For functional studies, there may be an advantage to leveraging existing consortia with expertise in specific tools, assays and approaches. Activity — particularly standards, quality control, resource development and data sharing — can be managed without being prematurely or overly prescriptive.

NHGRI needs to take the title of the workshop to heart and expand beyond genome sequencing. This will include functional studies, as discussed, as well as opportunities for large-scale efforts in epigenomics and metabolomics.
NHGRI should strive to put the “W” back in whole genome sequencing (WGS). This includes considering how the WGS as done today differs from perfection (i.e., phased telomere to telomere contiguity), articulating what is missing in current technologies, and specifying what could be enabled by alternative technologies. This topic is sometimes overlooked, since it is viewed as solved, or passé, but is an area that could benefit from more investment and creativity. Cases who currently go undiagnosed through routine sequencing for Mendelian disorders and other clinical phenotypes should be assessed with respect to the potential role of structural variants and other missing sequence data.
NHGRI programs all require advances and investment in bioinformatics, biocomputing and data science. Needs in this area should be considered in the design of research programs and funding opportunity
announcements. Projects need to have the right size and balance of expertise, along with sufficient resources and support, in
bioinformatics, biocomputing and data science.

Human disease is a perturbation of systems. Systems biology approaches should be incorporated into studies. The role of genetic variants needs to be appreciated in the larger context of the cell, the individual and the environment, which can be achieved through continued studies of gene-gene and gene-environment interactions and pathways.


An hereditary meritocracy

March 2, 2015

An hereditary meritocracy http://www.economist.com/news/briefing/21640316-children-rich-and-powerful-are-increasingly-well-suited-earning-wealth-and-power The rich gaming college admissions? Public good in progressive aid stemming from a $1M gift

The fierce competition between universities to build endowments makes doing such favours for alumni enticing. And there is a public-good argument for it: a student who comes with $1m attached can pay for financial aid for many others. But in practice this is not how the system works. While it is true that some elite universities are rich enough to give out a lot of financial support, people who can pay the full whack are still at the centre of the business model for many. Mitchell Stevens, a Stanford sociologist who spent a year working in the admissions office of an unnamed liberal arts college in the north-east, found that the candidate the system most prized was one who could pay full tuition and was just good enough to make one of the higher-profile sports teams but had a strong enough academic record not to eat into the annual allocation reserved for students whose brains work best when encased in a football helmet.


Six takeaways from that epic Jony Ive profile

March 2, 2015

6 takeaways from that epic…Ive profile http://mashable.com/2015/02/17/jony-ive-new-yorker-profile/ Perhaps peaking at $APPL’s 3k SF design nexus reveals too much, esp on watch

odrive | How odrive works – Mac — odrive

March 1, 2015

interesting app to sync multiple cloud drives

This is the best explanation of gerrymandering you will ever see – The Washington Post

March 1, 2015


Leonard Nimoy, Spock of ‘Star Trek,’ Dies at 83 – NYTimes.com

March 1, 2015



March 1, 2015

interesting combo of bio & soc networks


The Clutter Cure’s Illusory Joy – NYTimes.com

March 1, 2015

The #Clutter Cure’s Illusory Joy
http://www.nytimes.com/2015/02/16/opinion/the-clutter-cures-illusory-joy.html “Robberies declined in rich countries…wasn’t worth risking prison for a $150 TV.”


Clutter is having its moment in part because we’ve accumulated a critical mass of it. The cascade began 25 years ago, when China started to export huge amounts of cheap clothes, toys and electronics. Cut-rate retailers and big-box stores encouraged us to stockpile it all.

And we did. A study of middle-class families in Los Angeles found that just one in four families could fit a car in its garage. (It also found that mothers’ stress levels rose as they described their household mess.) Americans who struggled to afford health insurance and college could nevertheless buy lots of stuff, sometimes on credit.

But as stuff got cheaper, it lost status. Robberies declined in rich countries, in part because it wasn’t worth risking prison for a $150 TV. Reality shows about hoarders made having lots of things even less appealing.


Steve Jobs: Walter Isaacson, Dylan Baker: 9781442369054: Amazon.com: Books

March 1, 2015

Some brief thoughts on @WalterIsaacson’s book on Steve Jobs. Great Biography of An Extreme Individual

Walter Isaacson’s biography of Steve Jobs is a fantastic read, both engaging and revealing in many details. What emerges is a portrait of a genius — but also a quirky person with many contradictions. On one hand, the visionary who brought us the Mac, the iPhone, the iTunes Store and many other exceptional innovations but also the taskmaster who was incredibly demanding and difficult to interact with — someone who would get upset at the smallest details. Of particular interest to fans of Apple products: there are many tidbits on how particular features (and bugs) got included — from the oval on the MacIntosh dialogue boxes to the band circling the iPhone 4. There is also much revealing information on how the CEO of a huge public company concealed his cancer from so many people and about the intricate boardroom interplay deposing a leader and then his comeback. Altogether, a great read that I would recommend to anyone.

Note tags bundle:



The Secret Life of Passwords – NYTimes.com

March 1, 2015



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