Category: Misc.

Organization plan of attack!

One thing I would like to do tomorrow is go through our boxes and organize all the DNA, PCR reactions, and final products by sample ID #. I also want to write on the boxes of DNA and PCR reactions which numbers are in that box. For example, we have two DNA boxes (and probably more to come), and it can be quite tedious finding a DNA sample when you don’t know which box it’s in and the ID #’s are written very small on the lids of the 2mL tubes. (You would feel the same way if you had my terrible vision!)  I also want to take the original samples out of the freezer and write on the box which samples are in that particular box. Those samples are in the negative 80 degree fridge and it can be quite painful sitting there opening and closing box after box looking for the write samples. Hopefully I get a chance to do that and hopefully it helps 🙂

WWWD – What would Wolbachia do? Not always male destruction. Not always mutualism. Sometimes they disappear.

Interesting paper in Nature Genetics: Genomics of Loa loa, a Wolbachia-free filarial parasite of humans : Nature Genetics : Nature Publishing Group.  It is “Open” due to the NPG policy for papers reporting genome data.

Anyway – the paper deals in parts with the biology of the interaction between Wolbachia and filiarial nematodes.  Wolbachia are these fascinating intracellular bacteria that are found to infect a diversity of invertebrate species.  In 2004 we published the genome sequence of the first Wolbachia genome – a strain that infects Drosophila melanogaster and causes male specific detrimental effects (see summary here and our paper here and a general review here).  Many of the Wolbacia that are well studied have male specific effects leading us to jokingly call them “WMDs” the Wolbachia of male destruction.

Interestingly, Wolbachia also infect filarial nematodes, such as the ones that cause various nasty diseases.  And these Wolbachia not only do not have any obvious male specific detrimental effects, they appear to be mutualistic symbionts of the nematodes.  That is where this paper comes in.  The authors sequenced the genome of a filarial nematode that does not have any Wolbachia.  The premise here is – if Wolbachia are needed for other nematodes maybe one can figure out what Wolbachia do by identifying features in the Wolbachia-free nematode that are not in the ones with Wolbachia. 

 They write

Loa loa, the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae, L. loa does not contain the obligate intracellular Wolbachia endosymbiont. We describe the 91.4-Mb genome of L. loa and that of the related filarial parasite Wuchereria bancrofti and predict 14,907 L. loa genes on the basis of microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite, Brugia malayi, and to those of several other nematodes, we demonstrate synteny among filariae but not with nonparasitic nematodes. The L. loa genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for use in humans. Despite lacking Wolbachia, L. loa shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role of Wolbachia in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and nonparasitic nematodes.

 Anyway – the paper is worth checking out.

Figure 3: Phylogenomic analysis of nematodes.. Maximum likelihood, parsimony and Bayesian methods all estimated an identical phylogeny using the concatenated protein sequences of 921 single-copy orthologs. To the left of each node are likelihood bootstrap support values/parsimony bootstrap support values/Bayesian posterior probabilities. The distributions of genes in the ortholog clusters are shown to the right of the phylogeny. Core genes are encoded by all genomes, shared genes are encoded by at least two but fewer than all genomes, and unique genes are found only in one genome. Orthologs specific to the nonparasitic (C. elegans, C. briggsae and P. pacificus) and filarial nematodes are also highlighted. Of the 6,280 L. loa genes with no functional assignment, 3,665 are unique to L. loa and 1,158 are filarial specific. From http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2585.html
——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

Human microbiome all over the news (well, the topic that is)

Just a quick post here.  In the last week or so the human microbiome has been all over the news.  Here are some links to check out

And many more …
——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

Just out from TED – Jessica Green on buildings and microbes

Go microbes:

  http://embed.ted.com/talks/jessica_green_good_germs_make_healthy_buildings.html

——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

HeLa genome sequenced w/o obtaining permission/consent from family – some comments and background

Last week David Coil in my lab reminded me that he had been wanting to borrow a copy of “The Immortal Life of Henrietta Lacks” by Rebecca Skloot.  I have read the book many many times and had told David I even had a preprint that Skloot or her publicist sent me before the book came out (I did not know Skloot then – I just got it because of my blog).  As I went to grab the preprint off my shelf in my office he said he wanted to read it know because the genome of the HeLa cells which had been taken from Mrs. Lacks had been published a few days before.  I was shocked.  I asked him if he knew if the authors of said paper had gotten consent before publishing it.  So I opened a web browser and googled and found the paper and some news stories and a press release from the group who did the sequencing.

Holy fuck.  They did not seem to have permission.  Uggh.  I had thought about this a lot because a few years ago I was thinking of writing a review of “The Immortal Life of Henrietta Lacks”. As part of that started to write about the possibility of sequencing the HeLa genome and what that might mean.  I also did an April Fools joke relating to the topic: http://therealhela.blogspot.com.  And every time new sequencing technology comes along I have thought about – and discussed with others – the possibility of sequencing the HeLa genome.  And every time I got to this point I decided that it would be unethical, inappropriate, and downright stupid to do this without consent.  Note – my original plans for the book review involved a focus on the strange balance between openness and sharing in the history of HeLa and the lack of consent (e.g., see this blog post).

I was so angry about the lack of consent here that I took to Twitter.

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And after that there was remarkably little discussion of the issue by others. What the fuck? People get up in arms about all sorts of minor things so why not get up in arms about this? Where were all the supposed genomic ethicists out there? How did this happen? Thankfully, yesterday a piece on the topic came out from Rebecca Skloot (it was in this mornings New York Times) and it has launched this issue into a much more public discussion. So much discussion that I decided to storify it. See below.

//storify.com/phylogenomics/hela-genome-sequenced-w-o-consent.js[View the story “#HeLa genome sequenced w/o consent (by Jonathan Eisen)” on Storify]

Lots of discussions going on out there. And I think Rebecca deserves credit for writing this piece and bringing the story out more. I tried to get people going on Twitter and it was a slog — people did not seem that interested to be honest. Now – everyone seems interested. Including some who say they agree with Rebecca (and me) that it was a mistake to publish this genome.

Alas, am wondering what these people thought before the Skloot article. Why did so many people just stand by and say nothing? Too busy? Did not occur to them that this could be an issue? Or something else.  Oh – and why did it not occur to Francis Collins and all the people behind encode that this could be an issue. They published a lot of genomic data from HeLa cells and never once asked for consent or apparently even thought about it.

Anyway – it’s about time we as a community got off our butts and started discussion how to deal with the ethics of personal genome data.  This data will be coming out more and more.  We need to figure out how to handle it and the consent issues around it.  And we also need to do a better job of figuring out what to do with samples for which consent was not given but which are used.  Should we stop using HeLa cells?  Possibly.  If we want consent to use them – who will give it?  I don’t know the answers.  But I do know one thing – science should not simply proceed forward just because these questions are hard to answer.  Publishing the genome without consent or talking to the family was a very very very bad idea given that the ethical issues around consent here are murky.

UPDATE – 5 PM 3/24/13

Adding some notes about the press release and genome publication
Genome paper: – some key quotes of interest
  • Abstract
    • “To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome”
    • “Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins.”
  • Results
    • “produced nearly 1 billion reads of length 101 nt” (thus they produced 101 billion bases of DNA sequence information).
    • The read data are available in the European Nucleotide Archive (ENA) database under the accession number ERP001427. 
    • We report a compendium of genomic variation (CN, SNVs and SVs) as well as the first HeLa genome draft, which are available as VCF and FASTA files respectively 
    • We provide a tool to perform the translation of coordinates between GRch37 and our HeLa reference, 
    • Most variants in these HeLa cells thus represent common variants in the human population. The African-American population (to which Henrietta Lacks belonged) is spread between the African and European clusters, with the HeLa sample overlapping both. This demonstrates that although the genomic landscape of HeLa is strikingly different from that of a normal human cell, the population-specific SNV patterns are still detectable. 
  • Discussion
    • Since the establishment of the HeLa cell line in 1952, it has been used as a model for numerous aspects of human biology with only minimal knowledge of its genomic properties. Here we provide the first detailed characterization of the genomic landscape of one HeLa line relative to the human reference genome 
Original press release (a copy of which I found here). 
  • “The results provide the first detailed sequence of a HeLa genome,” explain Jonathan Landry and Paul Pyl from EMBL, who carried out the research. “It demonstrates how genetically complex HeLa is compared to normal human tissue. Yet, possibly because of this complexity, no one had systematically sequenced the genome, until now.”
  • “The HeLa genome had never been sequenced before, and modern molecular genetic studies using HeLa cells are typically designed and analysed using the Human Genome Project reference. This, however, misrepresents the sequence chaos that characterises HeLa cells, since they were derived from a cervical tumour and have since been adapting in laboratories for decades.”
  • “The study provides a high-resolution genetic picture of a key research tool for human biology. It highlights the extensive differences that cell lines can have from the human reference, indicating that such characterisation is importahttp://www.nytimes.com/2013/03/24/opinion/sunday/the-immortal-life-of-henrietta-lacks-the-sequel.html?_r=0nt for all research involving cell lines and could improve the insights they deliver into human biology.”
  • Can we infer anything about Henrietta Lacks or her descendants from this sequencing?
    • No, we cannot infer anything about Henrietta Lacks’ genome, or of her descendants, from the data generated in this study. Firstly, the subtype of HeLa cells sequenced in this study has spent decades in labs, dividing and thus undergoing mutations and changes – they are very different from the original cells that started growing in 1951. Secondly, these initial HeLa cells were taken from Henrietta Lacks’ cervical cancer tumour – as cancer is a disease of the genome, the DNA of cancer cells is usually different to that of the patient. Without any genetic information from the http://www.genomeweb.com/blog/learnt-lessonsoriginal tumour or from Henrietta Lacks, it is impossible to distinguish which parts of the genome sequenced here originate from Mrs. Lacks, her tumour, or laboratory adaptation. The goal of this study was not to gain insights into Henrietta Lacks’ cancer or personal biology, but rather to provide a resource for researchers using HeLa cells.

UPDATE 3: 11: 40 PM 3/25/13 Presidential Commission

Rebecca Skloot has unearthed a report from the Presidential Commission on for the Study of Bioethical Issues which few people seem to have been aware of (I have heard nothing about it). 

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The report was release on October 2012 but got very very little coverage and I have never seen/heard it mentioned anywhere. But it covers a lot of ground of direct relevance to this HeLa story. The whole report is available here. Here are some choice statements (bolding by me)

“Large-scale collections of genomic data raise serious concerns for the indi- viduals participating. One of the greatest of these concerns centers around privacy: whether and how personal, sensitive, or intimate knowledge and use of that knowledge about an individual can be limited or restricted (by means that include guarantees of confidentiality, anonymity, or secure data protec- tion). Because whole genome sequence data provide important insights into the medical and related life prospects of individuals as well as their relatives— who most likely did not consent to the sequencing procedure—these privacy concerns extend beyond those of the individual participating in whole genome sequencing. These concerns are compounded by the fact that whole genome sequence data gathered now may well reveal important information, entirely unanticipated and unplanned for, only after years of scientific progress.”

“Whole genome sequencing dramatically raises the privacy stakes because it necessarily involves examining and sharing large amounts of biological and medical information that is not only inherently unique to a single person but also has implications for blood relatives. Genomic information is inherited and determines traits like hair and eye color. Unlike a decision to share our hair or eye color, which does not reveal anything about our relatives that is not observable, a decision to learn about our own genomic makeup might inadvertently tell us something about our relatives or tell them something about their own genomic makeup that they did not already know and perhaps do not want to know. More than other medical information, such as X-rays, our genomes reveal something both objectively more comprehensive and subjectively (to many minds) more fundamental about who we are, where we came from, and the health twists and turns that life might have in store for us.”

“Because whole genome sequence information directly implicates relatives, psychological harms often are not limited to the person whose genome is voluntarily being sequenced and publicly disclosed. Even individuals who learn that they do not carry a harmful variant may experience “survivor’s guilt” if another family member is affected.”

“At the same time, individuals have a responsibility to safeguard their privacy as well as that of others, by giving thoughtful consideration to how sharing their whole genome sequencing data in a public forum might expose them to unwanted incursions upon their privacy and that of their immediate relatives. To be indifferent to the implica- tions of disclosure of sensitive data and information about one’s self is to act irresponsibly. That being said, it can be good and virtuous to share sensitive data about oneself in appropriate circumstances, for example, for the good of public health research or public education.”

“Risks might also fall to blood relatives of these individuals who carry similar genomic variants, thereby raising the stakes of privacy concerns in whole genome sequencing compared with most other types of research.”

UPDATE 4: 3/26/13 – Some new stories / links

UPDATE 5: 3/26/13 – Rebecca Skloot on Morning Edition

UPDATE 6: 3/26/13 – Some more stories / discussion

UPDATE 7: 3/26/13 2 PM PST Still waiting for ENCODE to say something about whether they are going to take down their #HeLa data. See for example my Tweet from a few days ago

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UPDATE 3/27

UPDATE 3/28
UPDATE 3/29
——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

Symposium on ADVANCEing STEM Faculty at #UCDavis 4/25 1-4 PM

UC Davis Consortium for Women and Research •
UC Davis Advance Program
Distinguished Women in Science Lecture Series

ADVANCEing STEM Faculty at UC Davis

A public symposium about the National Science Foundation ADVANCE program

Welcome by Provost Ralph Hexter Keynote by Chancellor Linda Katehi

Thursday April 25, 2013

1-4pm, with reception to follow ARC Ballroom A, UC Davis

For the past 20 years, the Distinguished Women in Science Lecture Series has showcased the work of top-ranking women scientists and explored the challenges facing women in STEM disciplines. This year the CWR is proud to partner with the UC Davis ADVANCE Program to present the 2013 Distinguished Women in Science Lecture Series in the form of a half-day symposium, “ADVANCEing STEM Faculty
at UC Davis.” The symposium will convene faculty, administrators, and students to discuss the national imperative for a diverse STEM faculty, the role the NSF ADVANCE Program plays in meeting that challenge, and the specific aims of the recently-established UC Davis ADVANCE Program lead by Chancellor Linda Katehi. Please join us to learn more about these issues and to welcome the ADVANCE effort to our campus.

Panel 1. “NSF ADVANCE: Goals, Impact, and Future”

  • Abigail Stewart, Sandra Schwartz Tangri Distinguished University Professor of Psychology and Women’s Studies, and Director of University of Michigan ADVANCE
  • Susan Carlson, UC Office of the President Vice Provost for Academic Personnel, Professor of English at UC Davis, PI of the NSF ADVANCE grant “Meeting the California Challenge”
  • Ruth Zambrana, Professor of Women’s Studies and Director of the Consortium on Race, Gender, and Ethnicity, University of Maryland, College Park

Panel 2. “ADVANCE Institutional Transformation at UC Davis”

  • Kim Shauman, Professor of Sociology, Co-PI and Faculty Director of UC Davis ADVANCE
  • Adela de la Torre, Interim Vice Chancellor of Student Affairs, Professor of Chicana/o Studies,
  • Director of the Center for Transnational Health at UC Davis, and Co-PI of UC Davis ADVANCE
  • Maureen Stanton, Vice Provost for Academic Affairs, Professor of Evolution and Ecology, and Co-PI of UC Davis ADVANCE

DWSLSFinalFlyer.pdf

Crosspost: New papers from our undergraduate “microbiology of the built environment” genome sequencing project

Crossposting from microBEnet.

We have two new papers out from our lab as part of our microBEnet supported undergraduate genome sequencing project:

Congratulations to all involved especially Jonathan Lo and Zack Bendiks, the undergrads who are first authors, and to David Coil who coordinated all the work.

More information about the project can be found on blog posts from my lab blog (https://phylogenomics.wordpress.com/category/undergraduate-genome-project/) and on a page here on microBEnet (http://www.microbe.net/undergraduate-research-built-environment-genomes/) and the YouTube video below:

 

.

In summary, the point of the project was to (1) start generating some reference genomes for microbes from the built environment and (2) to engage undergraduates at UC Davis in genome sequencing and microbiology of the built environment projects.

The papers are published in a new open access journal from the American Society for Microbiology called “Genome Announcements”.

Thanks also to the Alfred P. Sloan Foundation which funds microBEnet and to the UC Davis Genome Center DNA Technologies Core facility which ran the sequencing.  More papers are coming.  Stay tuned.

——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

Open source software tool for the week: AXIOME: automated exploration of microbial diversity

Just found this paper via Google Scholar Updates:
GigaScience | Abstract | AXIOME: automated exploration of microbial diversity

From Josh Neufeld’s lab this paper describes a series of tools for automation of microbial diversity analyses.

Abstract:
BackgroundAlthough high-throughput sequencing of small subunit rRNA genes has revolutionized our understanding of microbial ecosystems, these technologies generate data at depths that benefit from automated analysis. Here we present AXIOME (Automation, eXtension, and Integration Of Microbial Ecology), a highly flexible and extensible management tool for popular microbial ecology analysis packages that promotes reproducibility and customization in microbial research.
FindingsAXIOME streamlines and manages analysis of small subunit (SSU) rRNA marker data in QIIME and mothur. AXIOME also implements features including the PAired-eND Assembler for Illumina sequences (PANDAseq), non-negative matrix factorization (NMF), multi-response permutation procedures (MRPP), exploring and recovering phylogenetic novelty (SSUnique) and indicator species analysis. AXIOME has a companion graphical user interface (GUI) and is designed to be easily extended to facilitate customized research workflows.
ConclusionsAXIOME is an actively developed, open source project written in Vala and available from GitHub (http://neufeld.github.com/axiome) and as a Debian package. Axiometic, a GUI companion tool is also freely available (http://neufeld.github.com/axiometic). Given that data analysis has become an important bottleneck for microbial ecology studies, the development of user-friendly computational tools remains a high priority. AXIOME represents an important step in this direction by automating multi-step bioinformatic analyses and enabling the customization of procedures to suit the diverse research needs of the microbial ecology community.

Workflows like this are what many many people need.  I note – I have not used this yet but it looks promising.  It has some parallels to the WATERS workflow package that came from my lab a few years ago (see more about it here: https://phylogenomics.wordpress.com/software/waters/.)  Alas WATERS is no longer being actively developed.  Anyway – AXIOME has additional features and certainly seems like it would be useful to many people.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

Wanted: examples of family friendly policies for tenure review

I am on a committee at UC Davis that is part of an National Science Foundation “ADVANCE” grant that UC Davis’ Chancellor Linda Katehi and others at UC Davis received last year.  The goal of the project is “increasing the participation of women, especially Latinas, in academic science, technology, engineering and mathematics careers.”

More about the UC Davis ADVANCE program

One of the things the committee I am on is charged with is looking into how the policies and practices of tenure review might differentially impact women and minorities.  So – related to that I am writing to ask if people out there have examples of what one might call “family friendly” policies relating to extending the amount of time one is allowed before tenure review occurs.  Some questions I would love answers to for various institutions:

  • What are the policy guidelines for tenure review?
  • Can the tenure clock be extended for family related issues (e.g., birth of a child, adoption of a child, dependent medical care, etc)?
  • What is the specific wording of such policies?
  • How are such policies explained to tenure review committees and letter writers?

For UC Davis here is what I have been able to find (well, with help from the other people on the committee)

I posted a quick request to Twitter earlier.

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Any other information would be great.  I am hoping to make this an “open discussion” of such issues rather than just an internal UC Davis discussion …
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——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–

Digging around in National Science Foundation "news" is mostly a lesson in science by press release

Last week I wrote about how the National Science Foundation was involved in a painful press release about microbial genomics and evolution: Ugg – story about gene transfer/evolution based on NSF press release has a NASA-esque smell.  Today after getting some emails from people about this I decided to look to see if this was unusual or just what NSF press releases tend to look like.

I went to this site: News – US National Science Foundation (NSF) and decided to look at the links for stories I might know something about.  Here are some of them – a mix of NSF Press Releases and Links to outside PRs.

Alas most of these have some issues – some more than others.  Going through them one by one

Untangling Life’s Origins.  Link to an outside PR about work supported by NSF.  Not so bad – some painful stuff in the PR like the following:

  • “They are not the standard trees that people see in phylogenetic analysis,” he said. “In phylogenetic analysis, usually the tips of the trees, the leaves, are organisms or microbes. In these, they are entire biological systems.”
  • But overall reasonably tolerable compared to the others.
Home Toxic Home.  Link to an outside PR.  Filled with really painful stuff. Some examples
  • “Most organisms would die in the volcanic sulfur pools of Yellowstone and Mount Etna. Robust simple algae call it home, and their secrets to survival could advance human medicine and bioremediation. ”  Everything could advance human medicine and just about any other topic if you stretch it.  And it is a big stretch to find any connections here.
  • “Michael Garavito, Michigan State University professor of biochemistry and molecular biology was part of a research team that revealed how primitive red algae use horizontal gene transfer, in essence stealing useful genes from other organisms to evolve and thrive in harsh environments. ”  Ahh.  Back to the same general story that got me riled up to begin with.  This also has the fun “primitive” reference for algae which are not in any obvious way primitive. 
  • “The algae’s membrane proteins are biologically quite interesting because they’re receptors and transporters, the same classes of proteins that play key roles in energy metabolism and human immune response,” said Garavito. “This has applications in human medicine because virtually all of the important pathways that contribute to disease treatment involve membrane proteins.” So let me get this straight.  The algae has membrane transporters and receptors.  And therefore it is relevant to studies of human disease because many diseases are due to problems in transporters and receptors.  So – what organism on the planet then would not be relevant?  Uggh. 
  • They then clarify “What makes the algae’s membrane proteins attractive as a model for humans is their robustness. Other traditional candidates, such as yeast, insect cell cultures and slime mold, are fragile. The algae give researchers extra time to manipulate and examine their membrane proteins.”  Oh.  I see.  So nobody has ever thought of this before.  No work has ever been done on organisms that are “robust” as a model system.  Like – say – thermophiles?  Wouldn’t that be cool (or hot) to work on.  
  • There is more. I will not cover it.
Genetic Study of House Dust Mites Demonstrates Reversible Evolution.  Outside PR that is just completely full of crap.
  • A few days ago I posted about this to Facebook and to Twitter.  
  • And it still riles me up.  Some lines to treasure:
  • In evolutionary biology, there is a deeply rooted supposition that you can’t go home again: Once an organism has evolved specialized traits, it can’t return to the lifestyle of its ancestors. 
How to Thrive in Battery Acid and Among Toxic Metals.  This is the specific PR that got me riled up to begin with.  Awful.
“True Grit” Erodes Assumptions About Evolution.  Actually this one seems OK.

While most of what I looked at that seemed painful was from outside groups – I wonder whether NSF does any screening of outside press releases before posting them to their News site.  Given how bad some of the NSFs press releases are I am not so sure how they deal with outside PR.  But why aren’t they linking to actual news stories by real journalists?  Instead they simply link to PRs from groups supported by NSF.  Yuck.

——–
This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

——–