Challenges in phylogenetic tree visualization

I recently read an excellent review by Roderic Page, on the challenges in phylogenetic tree representation and visualization. It provides an overview  on existing software and tools (although he missed our ETE package, see image below for an example of ETE's visualization features). The number and diversity of existing tools is overwhelming, but probably matches the diversity of different interests and possible applications of phylogenetic trees. One may be interested in  overlaying sequence information (see below), while other would be interested in displaying information on the geographical distribution of the species. Some may need to represent uncertainty and overly different topologies, or networks to represent transfers of genetic material, the possibilities are unlimited.

 Most importantly he mentions some of the challenges of tree visualization software such as the ability to represent huge trees and to allow interactive behavior with the user. In our group we have encountered such needs and this is the reason behind implementing more visualization features in ETE. Fortunately new technologies are offering new opportunities as well, and I enjoyed imagining the possibilities that 3D visualization and touchscreen technologies will provide to researchers. Definitely is a field to follow.

 If you are interested in the topic. I recommend this video.

Phylogenetic Tree Challenge in Encyclopedia Of Life

 The Encyclopedia of Life initiative aims at providing an open, digital resource providing comprehensive information about the diversity of life. It has recently opened a call for teams that can provide a phylogeny-aware organization of as many scientific names as possible. This text is from the call:

A prize is offered to the individual or team that can provide a very large, phylogenetically-organized set(s) of scientific names suitable for ingestion into the Encyclopedia of Life as an alternate browsing hierarchy.  

[...]

Among other factors, the total number of uniquely named nodes, node/leaf ratios and tree height may be used to compare entries so contestants should consider how they wish to trade off strict consensus versus other methods of reflecting the state of phylogenetic knowledge.

Problems to solve include 1) how to assign labels to unnamed nodes, 2) how to fill in gaps so that the set of taxa included is as comprehensive as possible, even if trees are not fully resolved or all taxa have not been analyzed, 3) how to handle competing hypotheses, 4) how to update the hierarchy at least annually.  

The winning submission must be available to EOL and others under an acceptable CC license if it is under copyright.  The tree need not be previously published in peer-reviewed form.
 
 and more information is available here.

  

Diversity arises whenever, wherever, and at whatever rate is advantageous

 This is the conclusion from a recent paper from the group of Mark Pagel, in which they analyzed a dataset of body sizes of 3,185 extant mammals in a phylogenetic context.

  They modeled the evolution of body sizes across the  phylogeny using a Bayesian approach that allows evolutionary rates to vary at every branch. 

This provided them with an idea of where burst of evolution (big shifts in sizes) had occurred. The main idea was to contrast a long-held hypothesis that the early radiation of mammals was accompanied by increased rates of body-size variation (i.e burst in species diversity coincided with burst in body-size). This was explained by the idea that mammals expanded into a largely-unoccupied niche which provided opportunities for diversification. When the niche was filled up, diversification and evolutionary rates decreased. 

  Results from this team are in stark contrast with such view, since they see bursts at many different places of the phylogeny, which are uncoupled with the early radiation of mammals. 

 Reading this paper was very useful to me since, I was by then preparing the evaluation of a PhD thesis by Victor soria-Carrasco (see some related paper here) on, precisely mammalian, diversification. In the thesis they found that most mammalian orders showed a decline in the rate of diversification (in terms of forming of new species), which may seem compatible with the idea of a niche being filled-up. This highlights the importance of properly delimiting what evolutionary rates we refer to (sequence variation, variation in some morphological character, speciation rate...), since we may reach apparently different conclusions. Complicating the issue further, one does not know whether niche limitation may select for or against diversification. 

 In any case it is comforting to see that the increasing amount of genetic, phylogenetic, and other type of data, as well as sophisticated models, enable us to explore such interesting issues at the edge between evolution, phylogenetics and ecology. I was really impressed by the works mentioned. 

ALPHY 2012: French-Spanish meeting on Bioinformatics and Evolutionary Genomics (March 19 -21, Banyuls-sur-Mer)

 I am glad to announce ALPHY 2012, which for the first time is jointly co-organized by French and Spanish researchers. I was very glad to be invited by my French colleagues to sit at the organizing committe. I think it is a great opportunity to join two communities with ample experience in phylogenetics-related research.

ALPHY is an annual meeting, organized in France since 1995, dedicated to the field of Bioinformatics and Comparative Genomics (ALPHY = ALignments and PHYlogeny). The main goal of this meeting is to promote informal exchanges in this highly multidisciplinary field, and to encourage young scientists to present their work. The official invitation follows, plus a very tempting picture of the location.

This year, ALPHY is co-organized by Spanish and French scientists, in the nice city of Banyuls. There will be two invited speakers (Henrik Kaessmann and Jose Castresana), and the program will be open to contributions for 20’ talks.
The registration to the meeting is free, but mandatory. Please use the link (top left of this page) to register. If you wish to present your work, submit your abstract in the registration form.
Important dates:

• Deadline for abstract submission: January 10 2012
• Deadline for registration : February 1st 2012

Hasta pronto – A bientôt – fins aviat - see you in Banyuls!

Educational video on the Tree of Life

In the blog of Jun-Hoe Lee, a former visiting student in my lab, I found this interesting video from Yale university on the Tree of Life and the efforts to reconstruct it.

  

I think it is a good piece for popular communication of science and conveys pretty reasonably well the problem. Of course, there are simplifications and some important aspects such as that of horizontal transfer of genes, symbioses, and their effects on the tree are not covered, but it provides an attractive and educational introduction to the problem of assembling the tree of life. 

On the "orthology conjecture"

 Hi,

 Jonathan Eisen has opened a thread in his blog to discuss the recent paper by Hahn and colleagues on the "ortholog conjecture"  You can read more about the discussions raised by this paper here.

This is what I wrote, a text which I had to split in three pieces in Eisen's blog given the word limit for comments!!

Hi

I appreciate the effort by Matthew Hahnn on explaining the story behind his paper on the so-called "Ortholog conjecture" and on facing some of the criticism. This paper attracted my interest as that of many others that work on or just use orthology. For instance it was chosen by one of my postdocs for our "Journal Club" meeting. And it was discussed during our last "Quest for Orthologs" meeting in Cambridge. I think is raising a necessary discussion and therefore I think is a good paper. This does not mean that I fully agree with the interpretation and conclusions ;-). I hope to modestly contribute to this debate with the following post.

I think one of the causes that this paper has caused so much debate is that the conclusions seem to challenge common practice (inferring function from orthologs), and could be interpreted as the need of changing the strategies of genome annotation. I think, however, that one should interpret carefully these results before start annotating based on paralogous proteins. As I will discuss below one of the problems is that we need to agree in what is the conjecture to then agree in how to test it. I see three main points that can be a source of confusion: i) the issue of what is actually stated by this conjecture, ii) the issue of annotation, and iii) the issue of time

1) What is the "ortholog conjecture"?
Or in other terms, when should we expect orthologs to be more likely to share function than paralogs?. Always? Of course not. All of us would agree that two recently duplicated paralogs are likely to be more similar in function than two distant orthologs, so it is obvious that the conjecture is not simply "orthologs are more similar in function than paralogs". In reality the expectation that orthologs are more likely to be similar in function than paralogs, as least this is how I interpret it, is directly related to the effect that duplication have on functional divergence. If gene duplication has some effect on functional divergence (even in not 100% of the cases), then, given all other things equal (divergence time, story of speciation/duplication events - except fpr the duplication defining the orthologs) one would expect orthologs to be more likely to conserve function.

I think this complexity is not well considered (by many authors, in general). Hahn refeers to the famous review of orthology by Koonin (2005) as the source for the term "ortholog conjecture". However, In that paper this conjecture is discussed always within the context of genes accross two particular species, whether in Hahn's paper it is taken as well to other contexts. Thus, the proper context in which to test this conjecture is only between orthologs and between-species paralogs. As we can see,  Red and purple lines in Hahn paper in figure2 do not show any clear difference.

 Secondly, Koonin was very cautions in his paper, stating that he was referring to "equivalent functions" and not exactly the same "function", correctly implying that the functional contexts would be different in the two different species. This brings me to the next point.

ii) annotation
If the expectation of functional conservation of orthologs refers to a given pair of species, then it makes no sense to test that expectation between paralogs within the same species and orthologs in different species. We were interested in this issue and it took us some effort to control for this "species" influence on the comparison, if you are interested you can read our paper on divergence of expression profiles between orthologs and paralogs (http://www.ncbi.nlm.nih.gov/pubmed/21515902)

As Hahn founds, and it was anticipated by Koonin in that review, there is a huge influence of the "species context", a big constraint of what fraction of the function is shared. Indeed I think is the dominant signal in Hahn's paper. Why is that? One possibility is that the functional context determines the function, I agree. However, we should not discard biases in how different communities working around a model species define processes and function, also the type of experiments that are usually done. For instance experimental inference from KO mutants might be common from mouse, but I guess is not the case in humans (!!). I think this may be having a big influence and might even be the dominant signal in Hahns paper.

Finally function has many levels and I expect subfunctionalization mostly affect lower levels (i.e. more specific). Biases may also
 exist in the level of annotation between species or between families of different size (contributing more or less to the orthologs/paralogs class).

Microarray data are less likely to be subject to biases (although some may exist), at least they should be expected to be free of "human interpretation biases" and so Hahn and colleaguies did well, in my opinion, of testing that dataset. It is important to note that for microarrays and for orthologs and between-species paralogs (which I think is the right frame for testing the conjecture) ortholgs are more likely to share an expression context. This is compatible to what we found in the paper mentioned above, and compatible with the orthology conjecture as stated by koonin (accross species)


iii) time
 Finally, one aspect which I think is fundamental is the notion of "divergence time". Since paralogs can emerge at different time-scales they are composed by a heterogeneous set of protein pairs. Most of comparisons of orthologs and paralogs (Hahn's as well) use sequence divergence as a proxy of time. However this is only a poor estimate, specially when duplications (as in here) are involved (we explored this issue in the past: http://www.ncbi.nlm.nih.gov/pubmed/21075746). This means that for a given divergence time paralogs may have larger sequence divergence than orthologs at the same divergence time, or otherwise (if gene conversion is playing a role). Is the conjecture based on sequence divergence or on divergence time?, I think the initial sense of using orthology to annotate accross species is based on the notion of comparing things at the same evolutionary distance. Thus basing our conclusions on divergence times might not be the proper way of doing it.

CONCLUSIONS AND PROPOSAL FOR RE-STATEMENT

To conclude, and with the intention of going beyond this particular paper,
I would finish by saying that the key to the problem lies on how we interpret the so-called "ortholog conjecture" or how are our expectations on how function evolves. What I get from re-reading Eugene Koonin's paper and how I am using that "assumption" in my day-to-day work is the following:

"Orthologs in two given species are more likely to share equivalent functions than paralogs between these two species"

Therefore the notion of "accross the same pair of species" is important and thus only part of the comparisons made by Hahn and colleagues could directly test this. Looking at the microarray and between-species comparisons data, the conjecture may even hold true!!

I, however, do think that the conjecture as stated above is limited and does not capture the complexity of orthology relationships. Indeed us, and many other researchers, are tuning the confidence of the orthology-based annotation based on whether the orthologs are one-to-one, one-to-many or many-to-many, even when orthologs are "super-orthologs" (with no duplication event in the lineages separating the two orthologs).

Since, the underlying assumption of the ortholog conjecture is that duplication may (not necessarily always) promote functional shifts, then many-to-many orthology relationships will tend to include  orthologous pairs with different functions.

 Thus I would re-state the conjecture (or expectation) as follows:

 "In the absence of additional duplication events in the lineages separating them, two orthologous genes from two given species are more likely to share equivalent functions than two paralogs between these two species"

 This would be a more conservative expectation, which is closer to the current use of orthology-based annotation that tends to identify one-to-one orthologs, rather than any type.

 When duplications start appearing in subsequent lineages thus creating one- or many-to-many orthology relationships, the situation is less clear. Following the assumption that duplications may promote functional divergence. Then one could expand the conjecture by "the more duplications in the evolutionary history separating two genes, the lower the expectation that these two genes would share equivalent functions".

 I wrote this contribution on the fly, and surely there are ways of expressing this in more appropriate terms. In any case I hope I made clear the idea that the conjecture emerges from the notion of duplications causing functional shifts and that our expectations will be clearer if expressed on those terms. This goes on the lines of what Jonathan Eisen mentioned on considering the whole phylogenetic story to annotate genes.

 Under this perspective, the real important hypothesis is that "duplications tend promote functional shifts", I think this is based on solid grounds and has been tested intensively in the past.  

 Cheers,

Toni Gabaldón

http://treevolution.blogspot.com

The best of....... SMBE2011

With this post I initiate a series that will highlight some talks or posters in (some of) the meetings I attend. I want to note from the very beginning that this is very subjective and is according to my own taste and interests. I hope, however, that these highlights may also be interesting for some of the readers of this blog.

 I came back recently from the last Society for Molecular Biology and Evolution meeting (SMBE 2011) in Kyoto, Japan. This meeting has been marked by the recent natural disaster of the 2011 earthquake that affected the nuclear power station of Fukushima and the attendance was significantly lower than recent SMBE meetings. (around 650 attendees as compared to 2000 in SMMBE2010 in Lyon). However, despite this, the quality of the meeting has been really high with plenty of interesting presentations in the form of posters or talks.

 The poster that most caught my attention was one presenting the "Centroid Wheel Tree" representation, who allows representing alternative topologies within the same phylogenetic tree.

Wheel Tree Representation

I still have to explore that possibility and how it differs from the more standard network representations, but it looks promising and fairly adequate to accomodate our interest in accounting for the topological variation within phylomes.  

Among the selected oral presentations, my favourite was that  from Shigehiro Kuraku (Konstanz University, Germany) on the debated positions of the two rounds of whole genome duplications in the early vertebrates.

 From the invited speakers I would choose the talk of Nancy Moran, which went through many fascinating examples of insect endosymbiotic bacteria showing extremely reduced genomes.

 And, finally, one of the interesting parts of the meeting was one special session organized to conmemorate Walter Fitch, who passed away earlier this year (see my previous post). It was iinteresting to hear of many annecdotes from Masatoshi Nei, who shared with him the efforts of initiating the Society for Molecular Biology and Evolution and the MBE journal.

Mashatoshi Nei commemorating Walter Fitch at SMBE 2011

 Of course these are just some very personal highlights from a very interesting meeting. I will most probably attend next SMBE 2012  meeting in Dublin.  

 PS- I just noted that my blog has surpassed the 1,000 visits, this is encouraging.

Brief introductory article to phylogenomics

I would like to share a brief introductory article to Phylogenomics and Genome Evolution that I wrote by request from the Roche Institute portal. The idea was to provide an overview to the general audience of what is phylogenomics about and what are the main challenges ahead.

The article is also available in Spanish.

Learn Neighbor Joining method in 1-minute video.

 Hi,

 Have a ruler, a pen, scissors and some tape and glue around?... enough to reconstruct the tree of apes!.

I came across a short video, which illustrates for the general public how to build a phylogenetic tree from pair-wise distances.  The video has been made by Hidetoshi Shimodaira, the guy behind CONSEL package. I am already using it for teaching purposes.

Will we have one on ML and Bayesian reconstruction?


http://www.youtube.com/watch?v=PwiWgVdJ4Y8

The father of orthology and paralogy concepts, passes off.

Last week Walter Fitch, a founder of the field of molecular evolution, passed off. He, among many other contributions to the field of Molecular evolution, coined the concepts of orthology and paralogy. Therefore, Fitch's seminal work provide the foundations of a big part of what I am doing now. He left us, but his work will still propel current research in phylogenetics and comparative genomics.

A PLoS currents for the Tree of Life

 I recently discovered that PLoS Currents has opened a new track for the Tree of Life: PLoS Currents: Tree Of Life.

 PLoS currents is yet another form of publishing scientific results. A small group of editors and reviewers reviews every paper to check that it is t is " a legitimate work of science and does not contain any obvious methodological, ethical or legal violations." If that's the case papers are published immediately (and indexed in Pubmed). Another novelty is that all the publication procedure is based on a web-based tool called google-knol.

 So far there are only 4 articles (or "knols"?) and they all seem pertinent to the topic, one of them was very useful to me, since it described a compilation of benchmark datasets for phylogeny. 

 It looks worth to keep an eye.

Useful tool:phylowidget

Hi, I wanted to share this finding (phylowidget) that is making my life easier with respect to collaborations with experimentalists that are not used to handle newick files.

 I used to send .pdf or .png figures in order to share the results on my phylogenetic analyses, but having the possibility to interactively work with the figure is much better.

 Now I can send a simple link in this way (a very simple example):

http://www.phylowidget.org/lite/index.html?tree='(A:0.1,B:0.2,(C:0.3,D:0.4):0.5);'

and your colleague will be able to explore it. You can play around with the layout and really generate cool images. If the tree is huge you will have to place the file somewhere and provide the URL to phylowidget. This project was developed by a student within the google's summer of code program, which highlights the interest of this initiative.

In the future we plan to have something similar implemented in ETE.