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Earlier this week US News and World Report (USNWR) released, for the first time, a global ranking of universities including rankings by subject area. In mathematics, the top ten universities are:

1. Berkeley
2. Stanford
3. Princeton
4. UCLA
5. University of Oxford
6. Harvard
7. King Abdulaziz University
8. Pierre and Marie Curie – Paris 6
9. University of Hong Kong
10. University of Cambridge

The past few days I’ve received a lot of email from colleagues and administrators about this ranking, and also the overall global ranking of USNWR in which Berkeley was #1. The emails generally say something to the effect of “of course rankings are not perfect, everybody knows… but look, we are amazing!”

BUT, one of the top math departments in the world, the math department at the Massachusetts Institute of Technology is ranked #11… they didn’t even make the top ten. Even more surprising is the entry at #7 that I have boldfaced: the math department at King Abdulaziz University (KAU) in Jeddah, Saudi Arabia. I’ve been in the math department at Berkeley for 15 years, and during this entire time I’ve never (to my knowledge) met a person from their math department and I don’t recall seeing a job application from any of their graduates… I honestly had never heard of the university in any scientific context. I’ve heard plenty about KAUST (the King Abdullah University of Science and Technology ) during the past few years, especially because it is the first mixed-gender university campus in Saudi Arabia, is developing a robust research program based on serious faculty hires from overseas, and in a high profile move hired former Caltech president Jean-Lou Chameau to run the school. But KAU is not KAUST.

A quick google searched reveals that although KAU is nearby in Jeddah, it is a very different type of institution. It has two separate campuses for men and women. Although it was established in 1967 (Osama Bin Laden was a student there in 1975) its math department started a Ph.D. program only two years ago. According to the math department website, the chair of the department, Prof. Abdullah Mathker Alotaibi, is a 2005 Ph.D. with zero publications [Update: Nov. 10: This initial claim was based on a Google Scholar Search of his full name; a reader commented below that he has published and that this claim was incorrect. Nevertheless, I do not believe it in any way materially affect the points made in this post.] This department beat MIT math in the USNWR global rankings! Seriously?

The USNWR rankings are based on 8 attributes:

– global research reputation
– regional research reputation
– publications
– normalized citation impact
– total citations
– number of highly cited papers
– percentage of highly cited papers
– international collaboration

Although KAU’s full time faculty are not very highly cited, it has amassed a large adjunct faculty that helped them greatly in these categories. In fact, in “normalized citation impact” KAU’s math department is the top ranked in the world. This amazing statistic is due to the fact that KAU employs (as adjunct faculty) more than a quarter of the highly cited mathematicians at Thomson Reuters. How did a single university assemble a group with such a large proportion of the world’s prolific (according to Thomson Reuters) mathematicians? (When I first heard this statistic from Iddo Friedberg via Twitter I didn’t believe it and had to go compute it myself from the data on the website. I guess I believe it now but I still can’t believe it!!)

In 2011 Yudhijit Bhattacharjee published an article in Science titled “Saudi Universities Offer Cash in Exchange for Academic Prestige” that describes how KAU is targeting highly cited professors for adjunct faculty positions. According to the article, professors are hired as adjunct professors at KAU for $72,000 per year in return for agreeing (apparently by contract) to add KAU as a secondary affiliation at ISIhighlycited.com and for adding KAU as an affiliation on their published papers. Annual visits to KAU are apparently also part of the “deal” although it is unclear from the Science article whether these actually happen regularly or not.

[UPDATE Oct 31, 12:14pm: A friend who was solicited by KAU sent me the invitation email with the contract that KAU sends to potential “Distinguished Adjunct Professors”. The details are exactly as described in the Bhattacharjee article:

From: "Dr. Mansour Almazroui" <ceccr@kau.edu.sa>
Date: XXXX
To: XXXX <XXXX>
Subject: Re: Invitation to Join “International Affiliation Program” at 
         King Abdulaziz University, Jeddah Saudi Arabia

Dear Prof. XXXX ,

Hope this email finds you in good health. Thank you for your interest. 
Please find below the information you requested to be a 
“Distinguished Adjunct Professor” at KAU.

1. Joining our program will put you on an annual contract initially 
   for one year but further renewable. However, either party can 
   terminate its association with one month prior notice.
2. The Salary per month is $ 6000 for the period of contract.
3. You will be required to work at KAU premises for three weeks in 
   each contract year. For this you will be accorded with expected 
   three visits to KAU.
4. Each visit will be at least for one week long but extendable as 
   suited for research needs.
5. Air tickets entitlement will be in Business-class and stay in Jeddah
   will be in a five star hotel. The KAU will cover all travel and living
   expenses of your visits.
6. You have to collaborate with KAU local researchers to work on KAU 
   funded (up to $100,000.00) projects.
7. It is highly recommended to work with KAU researchers to submit an 
   external funded project by different agencies in Saudi Arabia.
8. May submit an international patent.
9. It is expected to publish some papers in ISI journals with KAU 
   affiliation.
10. You will be required to amend your ISI highly cited affiliation 
    details at the ISI
    highlycited.com 
    web site to include your employment and affiliation with KAU.

Kindly let me know your acceptance so that the official contract may
be preceded.

Sincerely,

Mansour

]

The publication of the Science article elicited a strong rebuttal from KAU on the comments section, where it was vociferously argued that the hiring of distinguished foreign scholars was aimed at creating legitimate research collaborations, and was not merely a gimmick for increasing citation counts. Moreover, some of the faculty who had signed on defended the decision in the article. For example, Neil Robertson, a distinguished graph theorist (of Robertson-Seymour graph minors fame) explained that “it’s just capitalism,” and “they have the capital and they want to build something out of it.” He added that “visibility is very important to them, but they also want to start a Ph.D. program in mathematics,” (they did do that in 2012) and he added that he felt that “this might be a breath of fresh air in a closed society.” It is interesting to note that despite his initial enthusiasm and optimism, Professor Robertson is no longer associated with KAU.

In light of the high math ranking of KAU in the current USNWR I decided to take a closer look at who KAU has been hiring, why, and for what purpose, i.e. I decided to conduct post-publication peer review of the Bhattacharjee Science paper. A web page at KAU lists current “Distinguished Scientists” and another page lists “Former Distinguished Adjunct Professors“. One immediate observation is that out of 118 names on these pages there is 1 woman (Cheryl Praeger from the University of Western Australia). Given that KAU has two separate campuses for men and women, it is perhaps not surprising that women are not rushing to sign on, and perhaps KAU is also not rushing to invite them (I don’t have any information one way or another, but the underrepresentation seems significant). Aside from these faculty, there is also a program aptly named the “Highly Cited Researcher Program” that is part of the Center for Excellence in Genomic Medicine Research. Fourteen faculty are listed there (all men, zero women). But guided by the Science article which described the contract requirement that researchers add KAU to their ISI affiliation, I checked for adjunct KAU faculty at Thomson-Reuters ResearcherID.com and there I found what appears to be the definitive list.

Although Neil Robertson has left KAU, he has been replaced by another distinguished graph theorist, namely Carsten Thomassen (no accident as his wikipedia page reveals that “He was included on the ISI Web of Knowledge list of the 250 most cited mathematicians.”) This is a name I immediately recognized due to my background in combinatorics; in fact I read a number of Thomassen’s papers as a graduate student. I decided to check whether it is true that adjunct faculty are adding KAU as an affiliation on their articles. Indeed, Thomassen has done exactly that in his latest publication Strongly 2-connected orientations of graphs published this year in the Journal of Combinatorial Theory Series B. At this point I started having serious reservations about the ethics of faculty who have agreed to be adjuncts at KAU. Regardless of the motivation of KAU in hiring adjunct highly cited foreign faculty, it seems highly inappropriate for a faculty member to list an affiliation on a paper to an institution to which they have no scientific connection whatsoever. I find it very hard to believe that serious graph theory is being researched at KAU, an institution that didn’t even have a Ph.D. program until 2012. It is inconceivable that Thomassen joined KAU in order to find collaborators there (he mostly publishes alone), or that he suddenly found a great urge to teach graph theory in Saudi Arabia (KAU had no Ph.D. program until 2012). The problem is also apparent when looking at the papers of researchers in genomics/computational biology that are adjuncts at KAU. I recognized a number of such faculty members, including high-profile names from my field such as Jun Wang, Manolis Dermitzakis and John Huelsenbeck. I was surprised to see their names (none of these faculty mention KAU on their websites) yet in each case I found multiple papers they have authored during the past year in which they list the KAU affiliation. I can only wonder whether their home institutions find this appropriate. Then again, maybe KAU is also paying the actual universities the faculty they are citation borrowing belong to? But assume for a moment that they aren’t, then why should institutions share the credit they deserve for supporting their faculty members by providing them space, infrastructure, staff and students with KAU? What exactly did KAU contribute to Kilpinen et al.  Coordinated effects of sequence variation on DNA binding, chromatin structure and transcription, Science, 2013? Or to Landis et al. Bayesian analysis of biogeography when the number of areas is large, Systematic Biology, 2013? These papers have no authors or apparent contribution from KAU. Just the joint affiliation of the adjunct faculty member. The limit of the question arises in the case of Jun Wang, director of the Beijing Genome Institute, whose affiliations are BGI (60%), University of Copenhagen (15%), King Abdulaziz University (15%), The University of Hong Kong (5%), Macau University of Science and Technology (5%). Should he also acknowledge the airlines he flies on? Should there not be some limit on the number of affiliations of an individual? Shouldn’t journals have a policy about when it is legitimate to list a university as an affiliation for an author? (e.g. the author must have in some significant way been working at the institution).

Another, bigger, disgrace that emerged in my examination of the KAU adjunct faculty is the issue of women. Aside from the complete lack of women in the “Highly Cited Researcher Program”, I found that most of the genomics adjunct faculty hired via the program will be attending an all-male conference in three weeks. The “Third International Conference on Genomic Medicine” will be held from November 17–20th at KAU. This conference has zero women. The same meeting last year… had zero women. I cannot understand how in 2014, at a time when many are speaking out strongly about the urgency of supporting females in STEM and in particular about balancing meetings, a bunch of men are willing to forgo all considerations of gender equality for the price of ~$3 per citation per year (a rough calculation using the figure of $72,000 per year from the Bhattacharjee paper and 24,000 citations for a highly cited researcher). To be clear I have no personal knowledge about whether the people I’ve mentioned in this article are actually being paid or how much, but even if they are being paid zero it is not ok to participate in such meetings. Maybe once (you didn’t know what you are getting into), but twice?!

As for KAU, it seems clear based on the name of the “Highly Cited Researcher Program” and the fact that they advertise their rankings that they are specifically targeting highly cited researchers much more for their delivery of their citations than for development of genuine collaborations (looking at the adjunct faculty I failed to see any theme or concentration of people in any single area as would be expected in building a coherent research program). However I do not fault KAU for the goal of increasing the ranking of their institution. I can see an argument for deliberately increasing rankings in order to attract better students, which in turn can attract faculty. I do think that three years after the publication of the Science article, it is worth taking a closer look at the effects of the program (rankings have increased considerably but it is not clear that research output from individuals based at KAU has increased), and whether this is indeed the most effective way to use money to improve the quality of research institutions. The existence of KAUST lends credence to the idea that the king of Saudi Arabia is genuinely interested in developing Science in the country, and there is a legitimate research question as to how to do so with the existing resources and infrastructure. Regardless of how things ought to be done, the current KAU emphasis on rankings is a reflection of the rankings, which USNWR has jumped into with its latest worldwide ranking. The story of KAU is just evidence of a bad problem getting worse. I have previously thought about the bad version of the problem:

A few years ago I wrote a short paper with my (now former) student Peter Huggins on university rankings:

P. Huggins and L.P., Selecting universities: personal preferences and rankings, arXiv, 2008.

It exists only as an arXiv preprint as we never found a suitable venue for publication (this is code for the paper was rejected upon peer review; no one seemed interested in finding out the extent to which the data behind rankings can produce a multitude of stories). The article addresses a simple question: given that various attributes have been measured for a bunch of universities, and assuming they are combined (linearly) into a score used to produce rankings, how do the rankings depend on the weightings of the individual attributes? The mathematics is that of polyhedral geometry, where the problem is to compute a normal fan of a polytope whose vertices encode all the possible rankings that can be obtained for all possible weightings of the attributes (an object we called the unitope). An example is shown below, indicating the possible rankings as determined by weightings chosen among three attributes measured by USNWR (freshman retention, selectivity, peer assessment). It is important to keep in mind this is data from 2007-2008.

unitope

 

Our paper had an obvious but important message: rankings can be very sensitive to the attribute weightings. Of course some schools such as Harvard came out on top regardless of attribute preferences, but some schools, even top ranked schools, could shift by over 50 positions. Our conclusion was that although the data collected by USNWR was useful, the specific weighting chosen and the ranking it produced were not. Worse than that, sticking to a single choice of weightings was misleading at best, dangerous at worse.

I was reminded of this paper when looking at the math department rankings just published by USNWR. When I saw that KAU was #7 I was immediately suspicious, and even Berkeley’s #1 position bothered me (even though I am a faculty member in the department). I immediately guessed that they must have weighted citations heavily, because our math department has applied math faculty, and KAU has their “highly cited researcher program”. Averaging citations across faculty from different (math) disciplines is inherently unfair. In the case of Berkeley, my applied math colleague James Sethian has a paper on level set methods with more than 10,000 (Google Scholar) citations. This reflects the importance and advance of the paper, but also the huge field of users of the method (many, if not most, of the disciplines in engineering). On the other hand, my topology colleague Ian Agol’s most cited paper has just over 200 citations. This is very respectable for a mathematics paper, but even so it doesn’t come close to reflecting his true stature in the field, namely the person who settled the Virtually Haken Conjecture thereby completing a long standing program of William Thurston that resulted in many of the central open problems in mathematics (Thurston was also incidentally an adjunct faculty member at KAU for some time). In other words, not only are citations not everything, they can also be not anything. By comparing citations across math departments that are diverse to very differing degrees USNWR rendered the math ranking meaningless. Some of the other data collected, e.g. reputation, may be useful or relevant to some, and for completeness I’m including it with this post (here) in a form that allows for it to be examined properly (USNWR does not release it in the form of a table, but rather piecemeal within individual html pages on their site), but collating the data for each university into one number is problematic. In my paper with Peter Huggins we show both how to evaluate the sensitivity of rankings to weightings and also how to infer bounds on the weightings by USNWR from the rankings. It would be great if USNWR included the ability to perform such computations with their data directly on their website but there is a reason USNWR focuses on citations.

The impact factor of a journal is a measure of the average amount of citation per article. It is computed by averaging the citations over all articles published during the preceding two years, and its advertisement by journals reflects a publishing business model where demand for the journal comes from the impact factor, profit from free peer reviewing, and sales from closed subscription based access.  Everyone knows the peer review system is broken, but it’s difficult to break free of when incentives are aligned to maintain it. Moreover, it leads to perverse focus of academic departments on the journals their faculty are publishing in and the citations they accumulate. Rankings such as those by USNWR reflect the emphasis on citations that originates with the journals, as so one cannot fault USNWR for including it as a factor and weighting it highly in their rankings. Having said that, USNWR should have known better than to publish the KAU math rankings; in fact it appears their publication might be a bug. The math department rankings are the only rankings that appear for KAU. They have been ommitted entirely from the global overall ranking and other departmental rankings (I wonder if this is because USNWR knows about the adjunct faculty purchase). In any case, the citation frenzy feeds departments that in aggregate form universities. Universities such as King Abdulaziz, that may reach the point where they feel compelled to enter into the market of citations to increase their overall profile…

I hope this post frightened you. It should. Happy Halloween!

[Update: Dec. 6: an article about KAU and citations has appeared in the Daily Cal, Jonathan Eisen posted his exchanges with KAU, and he has storified the tweets]

The Genotype-Tissue Expression (GTEx) project is an NIH initiative to catalog human tissue-specific expression patterns in order to better understand gene regulation (see initial press release). The project is an RNA-Seq tour-de-force: RNA extracted from multiple tissues from more than 900 individuals is been quantified with more than 1,800 RNA-Seq experiments. An initial paper describing the experiments was published in Nature Genetics earlier this year and the full dataset is currently being analyzed by a large consortium of scientists.

I have been thinking recently about how to analyze genotype-tissue expression data, and have been looking forward to testing some ideas. But I have not yet become involved directly with the data, and in fact have not even submitted a request to analyze it. Given the number of samples, I’d been hoping that some basic mapping/quantification had already been done so that I could build on the work of the consortium. But, alas, this past week I got some bad news.

In a recent twitter conversation, I discovered that the program that is being used by several key GTEx consortium members to quantify the data is Flux Capacitor developed by Michael Sammeth while he was in Roderic Guigós group at the CRG in Barcelona.

What is Flux Capacitor?

Strangely, the method has never been published, despite the fact that it has been used in ten publications over the course of four years, including high profile papers from consortia such as ENCODE, GENCODE, GEUVADIS and GTEx. There is no manuscript on the author’s website or in a preprint archive. There is a website for the program but it is incomplete and unfinished, and contains no coherent explanation of what the program does. Papers using the method point to the article S. B. Montgomery, … , E. T. DermitzakisTranscriptome genetics using second generation sequencing in a Caucasian population, Nature 464 (2010) and/or the website http://sammeth.net/confluence/display/FLUX/Home for a description of the method. Here is what these citations amount to:

The Montgomery et al. paper contains one figure providing the “FluxCapacitor outline”. It is completely useless in actually providing insight into what Flux Capacitor does:

Splicing_graph

Modification of the top half of Supplementary Figure 23 from Montgomery et al (2010) titled “Flux Capacitor Outline” (although it actually shows a splice graph if one corrects the errors as I have done in red).

The methods description in the Online Methods of Montgomery et al. can only be (politely) described as word salad. Consider for example the sentence:

In our approach we estimate the biases characteristic of each experiment by collecting read distribution profiles in non-overlapping transcripts, binned by several transcript lengths and expression levels. From these profiles, we estimate for each edge and transcript a flux correction factor b^j_i that following the language of hydro-dynamic flow networks, we denote as the capacity of the edge, as the area under the transcript profile between the edge boundaries (Supplementary Fig. 23).

The indices and j for b^j_i are never defined, but more importantly its completely unclear what the the correction factor actually is, how it is estimated, and how it is used (this should be compared to the current sophistication of other methods). On the program website there is no coherent information either. Here is an example:

The resulting graph with edges labelled by the number of reads can be interpreted as a flow network where each transcript representing a transportation path from its start to its end and consequently each edge a possibly shared segment of transportation along which a certain number of reads per nucleotide — i.e., a flux — is observed.

I downloaded the code and it is undocumented- even to the extent that it is not clear what the input needs to be or what the output means. There is no example provided with the software to test the program.

I therefore became curious why GTEx chose Flux Capacitor instead of many other freely available tools for RNA-Seq (e.g. ALEXA-SeqCLIIQCufflinks, eXpress, iReckon IsoEM, IsoformExMISO, NEUMARSEM, rSEQrQuantSLIDE, TIGAR, …). Although many of these programs are not suitable for production-scale analysis, Cufflinks and RSEM certainly are, and eXpress was specifically designed for efficient quantification (linear in the number of mapped reads and constant memory). I looked around and no benchmark of Flux Capacitor has ever been performed–there is literally not even a mention of it in any paper other than in manuscripts by Sammeth, Guigó or Dermitzakis. So I thought that after four years of repeated use of the program in high profile projects, I would take a look for myself:

After fumbling about with the barely usable Flux Capacitor software, I finally managed to run it on simulated data generated for my paper: Adam Roberts and Lior Pachter, Streaming fragment assignment for real time analysis of sequencing experiments, Nature Methods 10 (2013), 71–73. One example of the state of the software is the example page (the required sorted file is posted there but its download requires the realization that is is linked to from the non-obviously placed paperclip). Fortunately, I was using my own reads and the UCSC annotation. The Roberts-Pachter simulation is explained in the Online Methods of our paper (section “Simulation RNA-Seq study”). It consists of 75bp paired-end reads simulated according to parameters mimicking real data from an ENCODE embryonic stem cell line. I tested Flux Capacitor with both 10 million and 100 million simulated reads; the results are shown in the figure below:

fc_plots

Flux Capacitor accuracy on simulations with 10 million and 100 million reads. The top panels show scatterplots of estimated transcript abundance vs. true transcript abundance. The lower panels show the same data with both axes logged.

For comparison, the next figure shows the results of RSEM, Cufflinks and eXpress on a range of simulations (up to a billion reads) from the Roberts-Pachter paper (Figure 2a):

Roberts-Pachter_Fig2a

Modification of Figure 2a from A. Roberts and L. Pachter, Nature Methods (2013) showing the performance of Flux Capacitor in context.

Flux Capacitor has very poor performance. With 100 million reads, its performance is equivalent to other software programs at 10 million reads, and similarly, with 10 million reads, it has the performance of other programs at 1 million reads. I think its fair to say that

Using Flux Capacitor is equivalent to throwing out 90% of the data!

The simulation is a best case scenario. It adheres to the standard model for RNA-Seq in which fragments are generated uniformly at random with lengths chosen from a distribution, and with errors. As explained above, all these parameters were set according to an actual ENCODE dataset, so that the difficulty of the problem corresponds to realistic RNA-Seq data. I can’t explain the poor performance of Flux Capacitor because I don’t understand the method. However my best guess is that it is somehow solving min-flow using linear programming along the lines of the properly fomulated ideas in E. Bernard, L. Jacob, J. Mairal and J.-P. VertEfficient RNA isoform identification and quantification from RNA-seq data with network flows, Technical Report HAL-00803134, March 2013. If this is the case, the poor performance might be a result of some difficulties resulting from the minimization of isoforms and reflected in the (incorrectly estimated) stripes on the left and bottom of the log-log plots. That is not to say the conclusions of the papers where Flux Capacitor is used are wrong. As can be seen from our benchmark, although performance is degraded with Flux Capacitor, the quantifications are not all wrong. For example, abundant transcripts are less likely to be affected by Flux Capacitor’s obviously poor quantification. Still, the use of Flux Capacitor greatly reduces resolution of low-expressed genes and, as mentioned previously, is effectively equivalent to throwing out 90% of the data.

As far as GTEx is concerned, I’ve been told that a significant amount of the analysis is based on raw counts obtained from reads uniquely mapping to the genome (this approach appears to have also been used in many of the other papers where Flux Capacitor was used). Adam Roberts and I examined the performance of raw counts in the eXpress paper (Figure S8, reproduced below):

Raw_reads_comparison

Figure S8 from A. Roberts and L. Pachter, Nature Methods (2013) showing the limits of quantification when ignoring ambiguous reads. NEUMA (Normalization by Expected Uniquely Mappable Areas) calculates an effective length for each transcript in order to normalize counts based on uniquely mappable areas of transcripts. We modified NEUMA to allow for errors, thereby increasing the accuracy of the method considerably, but its accuracy remains inferior to eXpress, which does consider ambiguous reads. Furthermore, NEUMA is unable to produce abundance estimates for targets without sufficient amounts of unique sequence. The EM algorithm is superior because it can take advantage of different combinations of shared sequence among multiple targets to produce estimates. The accuracy was calculated using only the subset of transcripts (77% of total) that NEUMA quantifies.

Quantification with raw counts is even worse than Flux Capacitor. It is not even possible to quantify 23% of transcripts  (due to insufficient uniquely mapping reads). This is why in the figure above the eXpress results are better than on the entire transcriptome (third figure of this post). The solid line shows that on the (raw count) quantifiable part of the transcriptome, quantification by raw counting is again equivalent to throwing out about 90% of the data. The dashed line is our own improvement of NEUMA (which required modifying the source code) to allow for errors in the reads. This leads to an improvement in performance, but results still don’t match eXpress (and RSEM and Cufflinks), and are worse than even Flux Capacitor if the unquantifiable transcripts are taken into account. In the recent Cufflinks 2 paper, we show that raw counts also cannot be used for differential analysis (as “wrong does not cancel out wrong”–  see my previous post on this).

One criticism of my simulation study could be that I am not impartial. After all, Cufflinks and eXpress were developed in my group, and the primary developer of RSEM, Bo Li, is now my postdoc. I agree with this criticism! This study should have been undertaken a long time ago and subjected to peer review by the author(s?) of Flux Capacitor and not by me. The fact that I have had to do it is a failure on their part, not mine. Moreover, it is outrageous that multiple journals and consortia have published work based on a method that is essentially a black box. This degrades the quality of the science and undermines scientists who do work hard to diligently validate, benchmark and publish their methods. Open source (the Flux Capacitor source code is, in fact, available for download) is not open science. Methods matter.

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