FUBAR - Fast Unconstrained Bayesian AppRoximation

From the authors that brought you BUSTED (Branch-site Unrestricted Statistical Test for Episodic Diversification), behold FUBAR: Fast Unconstrained Bayesian AppRoximation. (Doubly from the authors in this case, as the first author gave the tip-off.)

Despite it’s intranym status, FUBAR gets an extra geek hat-tip for being a homonym of “foo bar”. (Although in looking that up, I came across the original FUBAR acronym, which is hopefully not reflective of their method!)

Abstract

Model-based analyses of natural selection often categorize sites into a relatively small number of site classes. Forcing each site to belong to one of these classes places unrealistic constraints on the distribution of selection parameters, which can result in misleading inference due to model misspecification. We present an approximate hierarchical Bayesian method using a Markov chain Monte Carlo (MCMC) routine that ensures robustness against model misspecification by averaging over a large number of predefined site classes. This leaves the distribution of selection parameters essentially unconstrained, and also allows sites experiencing positive and purifying selection to be identified orders of magnitude faster than by existing methods. We demonstrate that popular random effects likelihood methods can produce misleading results when sites assigned to the same site class experience different levels of positive or purifying selection–an unavoidable scenario when using a small number of site classes. Our Fast Unconstrained Bayesian AppRoximation (FUBAR) is unaffected by this problem, while achieving higher power than existing unconstrained (fixed effects likelihood) methods. The speed advantage of FUBAR allows us to analyze larger data sets than other methods: We illustrate this on a large influenza hemagglutinin data set (3,142 sequences). FUBAR is available as a batch file within the latest HyPhy distribution (http://www.hyphy.org), as well as on the Datamonkey web server (http://www.datamonkey.org/).

• Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL & Scheffler K (2013). FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol Biol Evol. 30(5):1196-205. PMID: 23420840

BUSTED - Branch-site Unrestricted Statistical Test for Episodic Diversification

This paper popped up in my PubCrawler feed today:

Murrell B et al. (2015). Gene-wide identification of episodic selection. Mol Biol Evol. 2015 Feb 19. pii: msv035.

We present BUSTED, a new approach to identifying gene-wide evidence of episodic positive selection, where the non-synonymous substitution rate is transiently greater than the synonymous rate. BUSTED can be used either on an entire phylogeny (without requiring an a priori hypothesis regarding which branches are under positive selection) or on a pre-specified subset of foreground lineages (if a suitable a priori hypothesis is available). Selection is modeled as varying stochastically over branches and sites, and we propose a computationally inexpensive evidence metric for identifying sites under episodic positive selection on any foreground branches. We compare BUSTED to existing models on simulated and empirical data. An implementation is available on www.datamonkey.org/busted, with a widget allowing the interactive specification of foreground branches.

From the Introduction, we find that BUSTED is indeed an orca-worthy contrived acronym: BUSTED - Branch-site Unrestricted Statistical Test for Episodic Diversification.

BLAST - Basic Local Alignment Search Tool

If there is one bioinformatics program that every biologist has heard of, it is BLAST: Basic Local Alignment Search Tool. In fact, BLAST is so popular and famous that many people probably don’t know that it is an acronym nor what it stands for; “to BLAST” has become a verb in common use. For non-biologists, BLAST is a homology search tool, which means that it finds similarities between biological (nucleotide or protein) sequences, and biologists will frequently “BLAST a sequence against a database” to find similar sequences.

The original BLAST algorithm is pretty old, which is part of the reason for its widespread fame. I’m not sure of the stats but the original Altschul et al. (1990) paper must be one of the most cited of all time.

• Altschul S, Gish W, Miller W, Myers E & Lipman D (1990). “Basic local alignment search tool”. Journal of Molecular Biology 215 (3): 403–410.

Certainly a worth addition to ORCA. (Although the main motivation for adding it is for the next post!) Given that BLAST works by fragmenting the query sequence into pieces for the initial search, I think that it rates at least as a post hoc.

EDGE - Evolutionarily Distinct and Globally Endangered

Joining FATE in the pantheon of conservation acronyms, EDGE stands for Evolutionarily Distinct and Globally Endangered. It is the focus of the EDGE of Existence project, “saving the world’s most extraordinary species”:

“The EDGE of Existence programme is the only global conservation initiative to focus specifically on threatened species that represent a significant amount of unique evolutionary history.

Using a scientific framework to identify the world’s most Evolutionarily Distinct and Globally Endangered (EDGE) species, the EDGE of Existence programme highlights and protects some of the weirdest and most wonderful species on the planet. EDGE species have few close relatives on the tree of life and are often extremely unusual in the way they look, live and behave, as well as in their genetic make-up. They represent a unique and irreplaceable part of the world’s natural heritage, yet an alarming proportion are currently sliding silently towards extinction unnoticed.”

EDGE species are on the edge, so EDGE is clear pre hoc.

h/t: The Infinite Monkey Cage podcast

CREATE - Coalition for Research into the Evolution of Australian Terrestrial Ecosystems

CREATE - the Coalition for Research into the Evolution of Australian Terrestrial Ecosystems is a foundation run by my faculty (Science) at the University of New South Wales:

The CREATE fund has been established to provide a focus for studies into the evolution of Australia’s Ecosystems, concentrating on the last 100 million years.

The main emphasis is on the lessons that can be learned from the past and how these can provide an understanding of the present and the key to our future.

I think that CREATE counts as ad hoc but given that the products of their research constitute a stream of explanatory problems for Creationists, perhaps it is an ironic backronym!

ASSET - Accelerated Segment Switch in Exons to alter Targeting

See the entry for RAVER. These guys had clearly tried so hard to contrive an acronym that was a dictionary word (surely it should really be ASSEAT?) that I thought they deserved their own entry.

ASSET - Accelerated Segment Switch in Exons to alter Targeting:

Doley R, Mackessy SP & Kini RM (2009).Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins. BMC Evol Biol. 9:146.

RAVER - Rapid Accumulation of Variations in Exposed Residues

Things are beginning to settle after my recent move to Australia and today’s PubCrawler alert contained a reminder that ORCA had been somewhat neglected over the past few weeks:

RAVER - Rapid Accumulation of Variations in Exposed Residues - is the acronym given to a new theory to explain the molecular evolution of “three-finger” (snake) toxins:

Sunagar K, Jackson TN, Undheim EA, Ali SA, Antunes A & Fry BG (2013). Three-Fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of Snake Venom Toxins. Toxins (Basel) 5(11):2172-2208.

Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they are theorised to undergo adaptive evolution, the underlying diversification mechanisms remain elusive. Here, we report the molecular evolution of different 3FTx functional forms and show that positively selected point mutations have driven the rapid evolution and diversification of 3FTx. These diversification events not only correlate with the evolution of advanced venom delivery systems (VDS) in Caenophidia, but in particular the explosive diversification of the clade subsequent to the evolution of a high pressure, hollow-fanged VDS in elapids, highlighting the significant role of these toxins in the evolution of advanced snakes. We show that Type I, II and III α-neurotoxins have evolved with extreme rapidity under the influence of positive selection. We also show that novel Oxyuranus/Pseudonaja Type II forms lacking the apotypic loop-2 stabilising cysteine doublet characteristic of Type II forms are not phylogenetically basal in relation to other Type IIs as previously thought, but are the result of secondary loss of these apotypic cysteines on at least three separate occasions. Not all 3FTxs have evolved rapidly: κ-neurotoxins, which form non-covalently associated heterodimers, have experienced a relatively weaker influence of diversifying selection; while cytotoxic 3FTx, with their functional sites, dispersed over 40% of the molecular surface, have been extremely constrained by negative selection. We show that the a previous theory of 3FTx molecular evolution (termed ASSET) is evolutionarily implausible and cannot account for the considerable variation observed in very short segments of 3FTx. Instead, we propose a theory of Rapid Accumulation of Variations in Exposed Residues (RAVER) to illustrate the significance of point mutations, guided by focal mutagenesis and positive selection in the evolution and diversification of 3FTx.

This is really a twofer, as RAVER itself is proposed as a replacement for ASSET, which is pretty weak as fitting words to acronyms goes: ASSET - Accelerated Segment Switch in Exons to alter Targeting:

Doley R, Mackessy SP & Kini RM (2009).Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins. BMC Evol Biol. 9:146.

Unless there are more snakes in banking or dance music than I realise, I think these must both be rated as ad hoc.