HGVS nomenclature

 Was recently asked about HGVS nomenclature reporting. The fun thing about biology is that there's going to be exceptions to the rule or some shenanigans that you didn't expect when setting out a rule. 

"The Human Genome Variation Society (HGVS) provides standardized recommendations for describing human sequence variants, which are widely accepted in the scientific community, especially in the practice of clinical molecular pathology.1 Use of the HGVS nomenclature system is a de facto recommendation for clinical reporting of sequence variants.2, 3 Being a core component of the clinical report, incorrect HGVS nomenclature can have a negative impact on patient care, such as misdiagnosis or clinical trial ineligibility. HGVS nomenclature has been traditionally computed manually by pathologists from Sanger sequencing electropherograms. However, manually computing HGVS nomenclature is time consuming, complex, and error prone, particularly with insertion and deletion (indel) variants, resulting in inconsistencies across laboratories."

Source:Clinical Implementation and Validation of Automated Human Genome Variation Society (HGVS) Nomenclature System for Next-Generation Sequencing–Based Assays for Cancer

In the 25th Anniversary Special Issue of Human Mutation, Den Dunnen et al. (2016) publish an update of the Human Genome Variation Society (HGVS) recommendations for the description of sequence variants (http://www.HGVS.org/varnomen). One of the issues discussed is how widespread HGVS nomenclature is used and, when used, whether published variant descriptions correctly follow the recommendations. An EGFR (OMIM# 131550) lung cancer testing scheme assessed in January 2016 by the United Kingdom National External Quality Assessment Scheme (UK NEQAS) for Molecular Genetics demonstrates the current variability in the use and interpretation of the HGVS guidelines by diagnostic laboratories based across the globe.

Source: HGVS Nomenclature in Practice: An Example from the United Kingdom National External Quality Assessment Scheme   

 

Shall explore this tool 

hgvs: A Python package for manipulating sequence variants using HGVS nomenclature: 2018 Update

https://github.com/biocommons/hgvs

Exploring the 1000 genome dataset with Hail on Amazon EMR and Amazon Athena

 Blog post from Roy Hasson

https://aws.amazon.com/blogs/big-data/genomic-analysis-with-hail-on-amazon-emr-and-amazon-athena/?nc1=b_rp

Genomics analysis has taken off in recent years as organizations continue to adopt the cloud for its elasticity, durability, and cost. With the AWS Cloud, customers have a number of performant options to choose from. These options include AWS Batch in conjunction with AWS Lambda and AWS Step Functions; AWS Glue, a serverless extract, transform, and load (ETL) service; and of course, the AWS big data and machine learning workhorse Amazon EMR.

For this task, we use Hail, an open source framework for exploring and analyzing genomic data that uses the Apache Spark framework. In this post, we use Amazon EMR to run Hail. We walk through the setup, configuration, and data processing. Finally, we generate an Apache Parquet–formatted variant dataset and explore it using Amazon Athena.

CIViC is an open access, open source, community-driven web resource for Clinical Interpretation of Variants in Cancer

CIViC's Role in Precision Medicine

Realizing precision medicine will require this information to be centralized, debated and interpreted for application in the clinic. CIViC is an open access, open source, community-driven web resource for Clinical Interpretation of Variants in Cancer. Our goal is to enable precision medicine by providing an educational forum for dissemination of knowledge and active discussion of the clinical significance of cancer genome alterations.

CIViC is a community-edited forum for discussion and interpretation of peer-reviewed publications pertaining to the clinical relevance of variants (or biomarker alterations) in cancer. These interpretations may include associations between molecular alterations (or lack of alteration) and one or more drugs, diagnoses, prognoses or other treatment decisions. These interpretations of clinical significance (or lack of clinical significance) are purely for research purposes. A finding of no interpretation does not necessarily indicate lack of relevance for any specific variant or biomarker alteration. Interpretations are not presented in ranked order of potential or predicted importance.These interpretations make no promise or guarantee of any clinical benefit (or lack of clinical benefit).

https://civic.genome.wustl.edu/#/home

Verily Life Sciences new hires

http://www.bizjournals.com/sanfrancisco/blog/biotech/2016/05/google-alphabet-goog-verily-life-sciences-amgen.html

I guess scouting a company's recruitment page to understand the projects is a universally common thing. Interestingly this page even has a word cloud from the LinkedIn Profiles to see where the hires are previously from.


The new hires reflect the scope of the few Verily projects Google/Alphabet has allowed to escape to the public so far: a contact lens venture with Novartis AG for diabetics to track blood glucose levels, its buyout of a company with a spoon that counters shaking by Parkinson's disease patients and the big picture Baseline study, a deep research project designed to define a healthy human being."The future of biotech, medical and tech is going to coalesce. We've seen that with medical sensors that do more than count steps, artificial intelligence and virtual reality," Topol said. "All these things are going to have a big impact in medicine. It's a natural evolution." excerpted from @SFBusinessTimes 

Free Imputation servers

Free imputation servers will allow anyone to use the full haplotype reference panel to impute missing genotypes in their data.  Users will be able to upload (pre-phased or unphased) genotype data to the server. Imputation will be carried out remotely on the server, and the imputed data will then be made available to the user. 

Prototype imputation servers are already available at 

https://imputation.sanger.ac.uk/

https://imputationserver.sph.umich.edu/

A prototype phasing server for phasing high coverage sequenced samples is available at

https://phasingserver.stats.ox.ac.uk/

Source: http://www.haplotype-reference-consortium.org/data-access

Freelancing in Bioinformatics? It's happening here...uBiome FASTQ

http://www.guru.com/jobs/ubiome-raw-data-fastq-files-analysis/1210516#proposalModal

Any takers to help walk this guy through analysing ubiome raw fastq files?

p.s. I wasn't aware that ubiome gives out fastq files?

C. Jimmy Lin talks about crowdsourced funded Genomics research

Have you heard of http://raregenomics.org/ ? They are a 'non-profit organization that gives families afflicted by rare genetic disorders access to genome sequencing and expert analysis. One can't help but notice the similarity to BGI-Shenzhen which is the 'first citizen-managed , non-profit research institute in China'. Perhaps this is the start of a trend for research that benefits citizens directly. Instead of getting/waiting for government funding / which complicates and slows down the research (see grant cycle) you can get funding directly from the ones that benefit. The tip of the iceberg is when publicly funded research is unavailable for public access without paying subscription fees.

Direct to consumer treatments and research for rare genetic disorders makes sense if you think about it. Getting funding for diabetes is likely easier and makes more economical sense since the dollars benefit a larger populace.
If you have a rare genetic disorder that might be limited to your family or a few families, you are kinda out of luck.
Your options are

1. doing the research yourself
2. convince your physician to take it up as a research project
3. offer your patient sample for others to research (not the best example but TED Fellow Salvatore Iaconese open sourced his brain cancer for a cure or art)
4. well now you can go to raregenomics

Citizen science is the latest trending topic/tag. From ecology projects like http://iseahorse.org/ and http://www.birds.cornell.edu/citsci/ to sequencing projects like uBiome to 'Bioinformatics as a game' like Phylo website it will be interesting to see how this plays out for research and science education as a trend. IMHO, you can only get rare genetics disorder research started as a non-profit now since the cost of sequencing isn't cheap enough yet (see 'A $1000 genome by 2013?' )



Related Links
'la cura, the cure' http://artisopensource.net/cure/

'Interview with C. Jimmy Lin'
http://blog.ted.com/2013/01/18/rare-gifts-fellows-friday-with-c-jimmy-lin/
http://tedfellows.posterous.com/rare-gifts-fellows-friday-with-c-jimmy-lin

Nature ENCODE: Explore the wealth of information about the project's key findings and numerous integrative analyses.

Nature ENCODE
Nature ENCODE: Explore the wealth of information about the project's key findings and numerous integrative analyses.
nature.com · Tweet this story

Translational Genomics Research Institute, personalised genomics to improve chemotherapy, cloud computing for pediatric cancer

I think it's fantastic that this is happening right now. Given that the cost of sequencing and computing is still relatively high, I can see how the first wave of personalized medicine will be lead by non-profit organizations. I am personally curious how this might pan out and would this be cost-effective for the patients ultimately? Would they be able to quantify it? 

Kudos for Dell for being a part of this exercise, though I wondered if they could have donated more to the data center or alternatively setup a mega cloud center and donate compute resources instead. Since i think the infrastructure and knowledge gleaned will be useful for their marketing and sales. 

http://www.hpcinthecloud.com/hpccloud/2012-02-29/cloud_computing_helps_fight_pediatric_cancer.html

Cloud technology is being used to speed computation, as well as manage and store the resulting data. Cloud also enables the high degree of collaboration that is necessary for science research at this level. The scientists have video-conferences where they work off of "tumor boards" to make clinical decisions for the patients in real-time. Before they'd have to ship hard drives to each other to have that degree of collaboration and now the data is always accessible through the cloud platform.


"We expect to change the way that the clinical medicine is delivered to pediatric cancer patients, and none of this could be done without the cloud," Coffin says emphatically. "With 12 cancer centers collaborating, you have to have the cloud to exchange the data."


Dell relied on donations to build the initial 8.2 teraflop high-performance machine. A second round of donations has meant a doubling in resources for this important work, up to an estimated 13 teraflops of sustained performance.


"Expanding on the size of the footprint means we can treat more and more patients in the clinic trial so this is an exciting time for us. This is the first pediatric clinic trial using genomic data ever done. And Dell is at the leading edge driving this work from an HPC standpoint and from a science standpoint."


The donated platform is comprised of Dell PowerEdge Blade Servers, PowerVault Storage Arrays, Dell Compellent Storage Center arrays and Dell Force10 Network infrastructure. It features 148 CPUs, 1,192 cores, 7.1 TB of RAM, and 265 TB Disk (Data Storage). Dell Precision Workstations are available for data analysis and review. TGen's computation and collaboration capacity has increased by 1,200 percent compared to the site's previous clinical cluster. In addition, the new system has reduced tumor mapping and analysis time from a matter of months to days.

Complete Khoisan and Bantu genomes from southern Africa : Article : Nature

http://www.nature.com/nature/journal/v463/n7283/full/nature08795.html

Just attended a very good lecture by Stephan Schuster, entitled "African Genomes: Charting Human Diversity"

He offered unbiased views / charts on the platform differences between 454, GAIIx, HiSeq, SOLiD for NGS sequencing coverage (which I think I should not repeat here). It points to the need to do sequencing on 2 different platforms to get a more accurate SNP list.

He also gave compelling reasons for getting a 20x coverage of Human genome done in 454 to complete the human genome (457 gaps in hg19). 

Yes, I often forget that the media / lay person thinks that the human genome is 'complete'. It's a often ignored 'secret' that actually it isn't. Maybe the next marketing ploy(i mean strategy) for emerging sequencing platforms would be to be THE ONE that actually finishes the human genome.

Incomplete lineage sorting patterns among human, chimpanzee, and orangutan suggest recent orangutan speciation and widespread selection [RESEARCH]

Incomplete lineage sorting patterns among human, chimpanzee, and orangutan suggest recent orangutan speciation and widespread selection [RESEARCH]

from Genome Research current issue by Hobolth, A., Dutheil, J. Y., Hawks, J., Schierup, M. H., Mailund, T.

1 person liked this

We search the complete orangutan genome for regions where humans are more closely related to orangutans than to chimpanzees due to incomplete lineage sorting (ILS) in the ancestor of human and chimpanzees. The search uses our recently developed coalescent hidden Markov model (HMM) framework. We find ILS present in ~1% of the genome, and that the ancestral species of human and chimpanzees never experienced a severe population bottleneck. The existence of ILS is validated with simulations, site pattern analysis, and analysis of rare genomic events. The existence of ILS allows us to disentangle the time of isolation of humans and orangutans (the speciation time) from the genetic divergence time, and we find speciation to be as recent as 9–13 million years ago (Mya; contingent on the calibration point). The analyses provide further support for a recent speciation of human and chimpanzee at ~4 Mya and a diverse ancestor of human and chimpanzee with an effective population size of about 50,000 individuals. Posterior decoding infers ILS for each nucleotide in the genome, and we use this to deduce patterns of selection in the ancestral species. We demonstrate the effect of background selection in the common ancestor of humans and chimpanzees. In agreement with predictions from population genetics, ILS was found to be reduced in exons and gene-dense regions when we control for confounding factors such as GC content and recombination rate. Finally, we find the broad-scale recombination rate to be conserved through the complete ape phylogeny.

Maybe we have to sequence everybody! Every fish! BGI Cloud

Bio-IT world ran an interesting article with this quote


“The data are growing so fast, the biologists have no idea how to handle this data,” says Li. “I think the Cloud will be the solution. We have to sequence more and more data. Maybe we have to sequence everybody! Every fish! The data keep growing and we need a lot of compute power to process.”
For Chen, there are three priorities for BGI Cloud:

• Connectivity: With partners across China and the world, “we’ve connected all the people and resources—the sequencers, the samples, the ideas, the compute power, and the storage together to make a greater contribution.”
• Scalability: Calling the explosion in next-gen sequencing (NGS) a “data tsunami,” Chen says BGI aims to provide the parallel computing resources to help users manage and process these datasets. “If you can’t do the analysis, it’s pointless. We use distributed computing technology in the bioinformatics area. We’re confident we can solve the scalability problem.”
• Reproducibility: Chen says bioinformatics researchers are happy to show their data and their pet program—SOAP, BWA, and so on. “That’s fine. But analysis is very complicated. The methodology he is actually using is a homemade pipeline. It’s very difficult to reproduce that result. We built this platform not only to solve the capability and connectivity of computing, we want to resolve the problems in reproducing designs and procedures.”

With new NGS gene assembly and SNP calling programs such as Hecate and Gaea about to be released (see, “In the Name of Gods”), Li says it was essential to develop a “run-time environment, a Web-based platform for Cloud storage and reference data, with a feature-rich GUI, and effective bioinformatics analysis software.”

Kevin: It would be interesting to see how Amazon and other cloud providers together with Galaxy (usegalaxy.org) will take to BGI's offering to produce reproducible data analysis. (commercial software providers aside). Also their offering comes at a strange time when NCBI is discontinuing SRA. Might BGI cloud fill up the void where SRA left? 

Everyone is trying to come up with a 'standard' workflow that everyone will adopt but I feel that the ecology of bioinformatics is that there's always another 'better' way to tweak that analysis. Custom analysis is a pet phrase of a lot of bench biologists. 

Every bioinformatician will know and remember their treasure trove of throw away scripts that worked beautifully but only once for that set of data. 

NGS alignment viewers, assembly viewers -warning pretty graphics ahead

Chanced upon this review of the visualization tools out there that can help you make biologists understand what you just did with their NGS data. I think assembly viewers is the best name for this category of tools. Since many of these not only support BAM but other assembly formats as well.
My vote goes to BamView for the most creative name. but for pretty visuals I have to agree with the author that Tablet takes the cake. Tablet DOES have the least obvious sounding name which makes it difficult to find on google.

Microsoft Biology Tools

http://research.microsoft.com/en-us/projects/bio/mbt.aspx

The Microsoft Biology Tools (MBT) are a collection of tools that enable biology and bioinformatics researchers to be more productive in making scientific discoveries. Some of the tools provided here take advantage of the capabilities of the Microsoft Biology Foundation, and are good examples of how you can use MBF to create other tools.


When I last visited the site, no tools were available and I didn't realised it was finally released. Definitely will try some of these tools just to satisfy curiosity but I doubt these will find widespread usage but that's just a personal opinion. 


Stuff that caught my eye
BL!P: BLAST in Pivot
False Discovery Rate
Microsoft Research Sequence Assembler
SIGMA: Large Scale Machine Learning Toolkit

Do post comments here if you have tested any of the tools and found them useful!

What's your BRCA status? Personal Genomics testing.

Do-it-yourself genetic testing
   How to test your BRCA status and why we need to prepare for the personal genomics age.
Genome Biology 2010, 11:404

Interesting read covering issues on personal genomics. Did you know that “the BRCA gene patents, which are held by Myriad Genetics, cover all known cancer-causing mutations in addition to those that might be discovered in the future.” How did that one slip through the patent office?? Not that it really matters “Currently Myriad charges more than $3000 for its tests on the BRCA genes, while sequencing one's entire genome now costs less than $20,000. Furthermore, once an individual's genome has been sequenced, it becomes a resource that can be re-tested as new disease-causing mutations are discovered. “


“Regardless of how easy it might be to test for mutations, the restrictive nature of the BRCA gene patents means that anyone wishing to examine any mutation in BRCA1 or BRCA2 will have to obtain permission from the patent holder Myriad Genetics. This restriction applies even if testing your own genome. If you wanted to look at other genes, you would have to pay license fees for any of them that were protected by patents. In practice, although it may seem absurd, this means that before scanning your own genome sequence, you might be required by law to pay thousands of license fees to multiple patent holders. “


This is complete hogwash! ( the concept that I have to pay genome-squatters (see cybersquatters) in the human genome, I would much rather pay for real estate on the moon! )



related posts
US clinics quietly embrace whole-genome sequencing @ Nature News
Commentary on Personal Genomics testing

Genome sizes

Compendium of links for gauging genome sizes (useful for calculating genome coverage)

My fav diagram to get a relative feel for the genome sizes
is from Molecular Biology of the Cell

  For which the image is reproduced here Figure 1-38   Genome sizes compared

There's other sources like

Wikipedia http://en.wikipedia.org/wiki/Genome_size
also see Comparison of different genome sizes

DOGS - Database Of Genome Sizes last modified Tuesday 16th of May 2006

Google images search for "genome sizes" for other lucky finds.

How a programmer views the human genome

Grabbed this fantastic description on the ultimate question in the galaxy.

The genome is the source of a program to build and run a human

But: the author is not available for comment

It’s 3GB in size

In a single line

Due to constant forking, there are about 7 billion different versions

It’s full of copy-and-paste and cruft

And it’s completely undocumented

Q: How do you debug it?

 

Brilliant

I agree!

I forgot there are 7 billion versions when actually only 1000 are publicly avail for download! Lol

Author is 

Jim Stalker, the Senior Scientific Manager in charge of vertebrate resequencing informatics at the Sanger center. Grabbed off Todd Smith's post

 

GenoCon: First-ever Contest in Rational Genome Design Based on Semantic-web Technology

Fascinating!
Original post here and here

The Bioinformatics And Systems Engineering (BASE), a division of RIKEN, Japan’s flagship research institute, is holding its first ever International Rational Genome Design Contest (GenoCon) on the semantic web. The contest makes use of an information infrastructure for life science research known as the RIKEN Scientists’ Networking System (SciNeS*2) and will take place between May 25 and September 30.
Tokyo, Japan (PRWeb UK) May 24, 2010 — The Bioinformatics And Systems Engineering (BASE), a division of RIKEN, Japan’s flagship research institute, is holding its first ever International Rational Genome Design Contest (GenoCon) on the semantic web. The contest makes use of an information infrastructure for life science research known as the RIKEN Scientists’ Networking System (SciNeS*2) and will take place between May 25 and September 30.

GenoCon: An international science and technology competition supporting future specialists in rational genome design for Synthetic Biology
First-ever contest in rational genome design based on semantic-web technology
Summary:
- A challenge for green innovation: rational genome design of a plant with an environmental detoxification function.
- Collection and sharing of genome-design theories and programs from researchers around the world.
- Web-based contest aimed at supporting a future generation of scientists – including a category for high-school students.
The Bioinformatics And Systems Engineering (BASE), a division of RIKEN, Japan’s flagship research institute, is holding its first ever International Rational Genome Design*1 Contest (GenoCon) on the semantic web. The contest makes use of an information infrastructure for life science research known as the RIKEN Scientists’ Networking System (SciNeS*2) and will take place between May 25 and September 30.
Built upon semantic web technology, GenoCon is the first contest of its kind, offering contestants the chance to compete in technologies for rational genome design. To succeed, contestants must make effective use of genomic and protein data contained in SciNeS database clusters to design DNA sequences that improve plant physiology. In the first GenoCon, contestants are asked to design a DNA sequence conferring to the model organism Arabidopsis thaliana the functionality to effectively eliminate and detoxify airborne Formaldehyde.

GenoCon also offers, in addition to categories for Japanese and international researchers and university students, a category specifically for high-school students. Just as ROBOCON (Robot Contest), GenoCon thus provides opportunities for young people to learn about the most cutting-edge science with a sense of pleasure, bringing intellectual excitement to the field of Life Science and supporting a future generation of scientists.
GenoCon will be accepting entries to the contest starting May 25, 2010 at the official GenoCon website: http://genocon.org/sw/wiki/en/cria196s1i/.
For more information, please contact:
Dr. Tetsuro Toyoda
Director, Bioinformatics And Systems Engineering(BASE) Division
RIKEN Yokohama Institute
Tel: +81-(0)45-503-9610 / Fax: +81-(0)45-503-9553
Planning Section
Yokohama Research Promotion Division
RIKEN Yokohama Institute
Tel: +81-(0)45-503-9117 / Fax: +81-(0)45-503-9113
Ms. Tomoko Ikawa (PI officer)
Global Relations Office
RIKEN
Tel: +81-(0)48-462-1225 / Fax: +81-(0)48-462-4715
Mail: koho(at)riken(dot)jp

178 Microbial Reference Genomes Associated with the Human Body

Venter Institute Scientists, Along with Consortium Members of the NIH's Human Microbiome Project, Sequence 178 Microbial Reference Genomes Associated with the Human Body

Researchers from the J. Craig Venter Institute, a not-for-profit genomic research organization, have published (along with other members of the National Institutes of Health (NIH) Human Microbiome Jumpstart Reference Strains Consortium), a catalog of 178 microbial reference genomes isolated from the human body.  Other members of the Consortium are: Baylor College of Medicine Human Genome Sequencing Center, the Broad Institute, and the Genome Center at Washington University. The paper is being published in the May 21 issue of the journal Science. 
The human body is teeming with a variety of microbial species. This collective community is called the human microbiome. The role these microbes play in human health and disease is still relatively unknown but likely very important. The NIH Human Microbiome Project was launched in 2007, as part of the National Institutes of Health’s (NIH) Common Fund’s Roadmap for Medical Research. It is a $157 million, five-year effort that will implement a series of increasingly complicated studies that reveal the interactive role of the microbiome in human health. 

Venter Institute Press Release 20th May

Knome invites researchers to apply for free sequencing and analysis of human exomes

I think there's nothing like the word 'free' that gets researchers to stand up and listen ;p

The 2010 KnomeDISCOVERY Research Awards
Knome invites researchers to apply for free sequencing and analysis of human exomes

Knome announces the launch of the KnomeDISCOVERY Research Awards, designed to spur novel discoveries by researchers working at the nexus of genomics and human health. Given annually, the KnomeDISCOVERY Research Awards will fund innovative projects that help reveal the genetic underpinnings of disease.

This year, Knome will award comprehensive sequencing and discovery-supportive analysis of a total of six (6) human exomes. These services will be distributed among three winning biomedical research groups, each of whom will use the award to study a pair of human exomes of their choice in order to answer a compelling biological question.