Posts Tagged ‘i0gspplan’

One of a Kind – New Yorker

July 7, 2015

One of a Kind Story of rare mutation in NGLY1, illustrates power of #socialmedia, quite relevant to @solvemendelian

Medical Dispatch JULY 21, 2014 ISSUE
One of a Kind
What do you do if your child has a condition that is new to science?

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.


Notes from NHGRI planning mtg. on Future Opportunities for Genome Sequencing and Beyond

August 3, 2014

Took lots of notes at the NHGRI planning meeting,

(session I was in

Saved “public” versions of these as a storified tweet-stream, viz:

Also tagged lots of sites & papers that I discovered at the meeting, viz:

My (very brief) talk from the meeting:

Some of my “private” notes (need passwords) are:

In pursuit of design principles of regulatory sequences – Nat Rev Genet

July 29, 2014

In pursuit of design principles of regulatory sequences

Michal Levo & Eran Segal

Nature Reviews Genetics 15, 453–468 (2014) doi:10.1038/nrg3684

Ecker mentions: Design principles of regulatory sequences … for schematics on how to follow up reg. variants #GSPfuture

Common Fund for 4D Nucleome Study

July 29, 2014

One of a Kind – New Yorker

July 29, 2014

Medical Dispatch JULY 21, 2014 ISSUE
One of a Kind
What do you do if your child has a condition that is new to science?

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

July 29, 2014

Lots of LOF! — Boenke mentions: LOF mutations in SLC30A8 protect against T2D Power of combining data for mult. variants #GSPfuture