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Publications

Scientific Publications in Population Genetics, Systems Biology, and Computer Science

Editing

Loewe L and Hill WG; editors (2010) "The population genetics of mutations: good, bad and indifferent.Philosophical Transactions of the Royal Society B volume 365, issue number 1544, pages 1149-1294, ISSN 0962-8436, ISBN: 978-0-85403-813-8. 

This collection of papers by influential scientists highlights many of the challenges that we face when trying to understand the evolution of life with a special view on mutations. 

URL: http://rstb.royalsocietypublishing.org/content/365/1544.toc

 

Software

Loewe L, Keel SA, Scheuer K, Ehlert K, Flores-Lorca I, Engbretson T, and Goldfinger J (2015) "Evolvix 0.3.1." evolvix.org.

Prototypic, declarative implementation of an early draft of the Evolvix model description language for mass-action models in biology.

URL: http://evolvix.org/download 

 

Refereed Publications

L29:     Loewe L (2016) "Systems in Evolutionary Systems Biology." The Encyclopedia of Evolutionary Biology (RM Kliman, ed.), pp. 297-318. Oxford Academic Press, Elsevier. 

Summarizing discussions of recent years, this review substantially updates my EvoSysBio framework paper [L14] by defining EvoSysBio much more precisely. It includes a long-term research agenda for cancer cell biology, antibiotics resistance evolution, and more. [L29] replaces [L14] as my best and most comprehensive introduction to EvoSysBio.

URL: http://dx.doi.org/10.1016/B978-0-12-800049-6.00184-0  

 

L28:     Loewe L, Scheuer KS, and Keel SA (2016) "Evolvix concept: BEST Names for semantic units increase semantic reproducibility and help combine complex biological models." Proc. of the Workshop on Data Science, Learning and Applications to Biomedical and Health Sciences (DSLA-BHS 2016), pp. 67-73, NYAS, New York City.

A sea of synonyms and the perpetual tension between expert abbreviations and the need of beginners for longer names that are easier to understand can make computing in biology very challenging. Here I present what Evolvix can do to help reduce this problem. 

URL:   https://www.nyas.org/BigDataHealth

https://sites.google.com/site/dslabhs2016/proceeding-papers

 

L27:     Ehlert K and Loewe L (2014) "Lazy Updating of hubs can enable more realistic models by speeding up stochastic simulations.Journal of Chemical Physics 141:204109, 20 pages. PMCID: PMC4255425.

Introduces a new trick for speeding up stochastic simulations in the presence of hub-molecules like ATP.

URL: http://dx.doi.org/10.1063/1.4901114  


L26:     Watterson S, Guerriero M-L , Blanc M, Mazein A, Loewe L, Robertson KA, Gibbs H, Shui G, Wenk MR, Hillston J, and Ghazal P (2013) "A model of flux regulation in the cholesterol biosynthesis pathway: Immune mediated graduated flux reduction versus statin-like led stepped flux reduction.Biochimie 95 (3):613-621

Improves on [L22] to explore new ways of controlling the cholesterol synthesis pathway.
URL: http://dx.doi.org/10.1016/j.biochi.2012.05.024   

 

L25:     McGaugh SE, Heil CSS, Manzano-Winkler B, Loewe L, Goldstein S, Himmel TL, and Noor MAF (2012) "Recombination Modulates How Selection Affects Linked Sites in Drosophila." PLoS Biology 10(11): e1001422. PMCID: PMC3496668

URL: http://dx.doi.org/10.1371/journal.pbio.1001422  

 

L24:     Modrzynska K, Creasey A, Loewe L, Cezard T, Martinelli A, Borges S, Cravo P, Blaxter M, Carter R, and Hunt P (2012) “Genome-wide re-sequencing defines mutations of complex chloroquine resistance in malaria.” BMC Genomics 13:106.

Uses evolution experiments and NextGen sequencing to identify resistance loci in mouse malaria parasites. I developed the approach to compute statistical significance in these noisy datasets. Follows [L21].
URL: http://www.biomedcentral.com/1471-2164/13/106

 

L23:     Loewe L (2012) "How evolutionary systems biology will help understand adaptive landscapes and distributions of mutational effects." Evolutionary Systems Biology: Advances in Experimental Medicine & Biology (O. Soyer, ed.) vol. 751, pp 399-410. Springer.

Overview of what mechanistic evolutionary systems biology could do, following [L14].
URL: http://www.springerlink.com/content/t240h2n4v5j61735/

 

L22:     Loewe L, Guerriero ML, Watterson S, Moodie S, Ghazal P, and Hillston J (2011) “Translation from the quantified implicit process flow abstraction in SBGN-PD diagrams to Bio-PEPA illustrated on the Cholesterol pathway.Transactions on Computational Systems Biology XIII, Priami, C et al. (eds), Lecture Notes in Bioinformatics LNBI 6575, pages 13-38.

Further improvements to the bridge from SBGN to Bio-PEPA as described in [L16] and application of the system to the cholesterol synthesis pathway. See also [L7n].
URL: http://dx.doi.org/10.1007/978-3-642-19748-2_2   

 

L21:     Hunt P, Martinelli A, Borges S, Modrzynska K, Creasey A, Rodrigues L, Beraldi D, Loewe L, Fawcett R, Kumar S, Thomson M, Trivedi U, Otto T, Pain A, Blaxter M, and Cravo P (2010) “Experimental evolution, genetic analysis and genome re-sequencing reveals the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites.” BMC Genomics 11:499 (13 pages).

Uses evolution experiments in the lab to identify resistance loci in mouse malaria parasites to help anticipate malaria evolution. I helped to compute statistical significance.
URL: http://www.biomedcentral.com/1471-2164/11/499

 

L20:     Haddrill PR, Loewe L, and Charlesworth B (2010) “Estimating the parameters of selection on nonsynonymous mutations in Drosophila pseudoobscura and D. miranda.Genetics 185:1381-1396.

Applies the method in [L6] to a much bigger dataset.
URL: http://www.genetics.org/cgi/content/abstract/185/4/1381

 

L19:     Loewe L and Hill WG (2010) “Introduction: The population genetics of mutations: good, bad and indifferent.Philosophical Transactions of the Royal Society B 365:1153-1167.

An overview of the population genetics of mutations that highlights future challenges.
URL: http://rstb.royalsocietypublishing.org/content/365/1544/1153

 

L18:     Waxman D and Loewe L (2010) “A stochastic model for a single click of Muller’s ratchet.”  Journal of theoretical Biology 264:1120-1132.

Explores a new approach to computing the rate of the ratchet and compares it to evolution@home simulations.
URL: http://dx.doi.org/10.1016/j.jtbi.2010.03.014

 

L17:     Akman OE, Guerriero M-L, Loewe L, and Troein C (2010) “Complementary approaches to understanding the plant circadian clock.” FBTC 2010 Workshop “From Biology to Concurrency and Back”, http://disi.unitn.it/~fbtc2010/ Electronic Proceedings in Theoretical Computer Science EPTCS 19:1–19, DOI: 10.4204/EPTCS.19.1

Further steps towards an evolutionary systems biology model of a circadian clock with entrainment. Contains a systems biology model of the Ostreococcus circadian clock with realistic parameter values. I contributed the mutational robustness analyses [see L13].
URL: http://arxiv1.library.cornell.edu/abs/1002.4661v1

 

L16:     Loewe L, Moodie S, and Hillston J (2009) "Quantifying the implicit process flow abstraction in SBGN-PD diagrams with Bio-PEPA.” CompMod 2009 workshop, http://combio.abo.fi/compmod09/, Electronic Proceedings in Theoretical Computer Science EPTCS 6:93-107, DOI: 10.4204/EPTCS.6.7

Builds a compiler that maps biochemical models from SBGN to Bio-PEPA to build a bridge from visual model construction to automated simulations. See also [L7n].
URL: http://arxiv.org/abs/0910.1410

 

L15:     Duguid A, Gilmore S, Guerriero ML, Hillston J, and Loewe L (2009) “Design and development of software tools for Bio-PEPA.” Proceedings of the 2009 Winter Simulation Conference (WSC’09 http://www.wintersim.org/), pp. 956-967,
eds.: Rossetti RMD, Hill RR, Johansson B, Dunkin A & Ingalls RG. Austin, Texas.

A description of how the Bio-PEPA modelling tools are organised to facilitate the automatic conversion of models between different mathematical and other formalisms.
URL: http://www.informs-sim.org/wsc09papers/091.pdf

 

L14:     Loewe L (2009) "A framework for evolutionary systems biology.BMC Systems Biology 3:27 (34 pages, designated ‘highly accessed’ by BMC from continuous traffic).

This is the definitive reference for my new mechanistic framework for evolutionary systems biology that brings together systems biology and evolutionary genetics to help understand adaptive landscapes and distributions of small mutational effects.
URL: http://www.biomedcentral.com/1752-0509/3/27/ 

 

L13:     Loewe L and Hillston J (2008) "The distribution of mutational effects on fitness in a simple circadian clock." Proceedings of the 6th International Conference on Computational Methods in Systems Biology, CMSB08, eds Heiner M & Uhrmacher AM, Rostock, Germany, published in: Lecture Notes in Bioinformatics 5307:156-175.

The first proof of concept for my new approach to evolutionary systems biology.
URL: http://dx.doi.org/10.1007/978-3-540-88562-7_14

 

L12:     Loewe L and Cutter A (2008) "On the potential for extinction by Muller’s Ratchet in Caenorhabditis elegans.BMC Evolutionary Biology 8:125 (13 pages).

Here I combined my theory [L7] and evolution@home results with the expertise of my collaborator on the worm C. elegans. Builds on [L11].
URL: http://www.biomedcentral.com/1471-2148/8/125

 

L11:     Loewe L and Lamatsch D (2008) "Quantifying the threat from Muller's ratchet in the Amazon molly (Poecilia formosa).BMC Evolutionary Biology 8:88 (20 pages, designated ‘highly accessed’ by BMC, peak after news coverage).

Here I combined my theory [L7] and evolution@home results with the expertise of my collaborator on the fish P. formosa. Building on older work I also explain how Muller’s ratchet theory can be applied to selfing species.
URL: http://www.biomedcentral.com/1471-2148/8/88

 

L10:     Loewe L (2007) "Evolution@home: observations on participant choice, work unit variation and low-effort global computing.Softw. Pract. & Exp. 37:1289-1318.

Describes the semi-automated global computing by evolution@home and what needs to be improved. Builds on [L3].
URL: http://doi.wiley.com/10.1002/spe.806

 

L9:     Loewe L and Charlesworth B (2007) "Background selection in single genes may explain patterns of codon bias.Genetics 175:1381-1393.

Explores the patterns that deleterious mutations can produce within genes.
URL: http://www.genetics.org/cgi/content/abstract/175/3/1381

 

L8:     Loewe L and Charlesworth B (2006) "Inferring the distribution of mutational effects on fitness in Drosophila.Biology Letters 2:426-430.

Compares different types of distributions and finds the log-normal type to perform best.
URL: http://dx.doi.org/DOI:10.1098/rsbl.2006.0481

 

L7:     Loewe L (2006) "Quantifying the genomic decay paradox due to Muller's ratchet in human mitochondrial DNA.Genetical Research 87:133-159.

The most rigorous analysis so far of the potential for mutational meltdown in human mitochrondria, a good pointer to much of the work on Muller’s ratchet and the most comprehensive list so far of all the processes that might help to prevent meltdown.
URL: http://dx.doi.org/10.1017/S0016672306008123

 

L6:     Loewe L, Charlesworth B, Bartolomé C, and Nöel V (2006) "Estimating selection on non-synonymous mutations.Genetics 172:1079-1092.

We introduce a new approach to estimate the distribution of mutational effects from diversity data in two species that does not depend on ancient demography. We find most new mutations are effectively deleterious but have selection coefficients that are well below the thresholds of what can be detected directly in experiments.
URL: http://www.genetics.org/cgi/content/abstract/172/2/1079

L5:     Loewe L (2004) "Response to comment on 'High deleterious genomic mutation rate in stationary phase of Escherichia coli.'Science 304:518d-518d.

I show that earlier criticism of my work [L4] is unjustified and how bacteria might cooperate to be more flexible.
URL: http://www.sciencemag.org/cgi/content/full/304/5670/518d  

 

L4:     Loewe L, Textor V, and Scherer S (2003) "High deleterious genomic mutation rate in stationary phase of Escherichia coli.Science 302:1558-1560.

The first mutation accumulation experiment in stationary phase. Like in all MA experiments, only large selection coefficients could be observed. This work uncovers complex evolutionary processes in stationary phase that have a wide range of implications that are best explored in computational models yet to be built.
URL: http://www.sciencemag.org/cgi/content/abstract/302/5650/1558

 

L3:     Loewe L (2002) "evolution@home: Experiences with work units that span more than 7 orders of magnitude in computational complexity." pp. 425-431 in Proceedings of the 2nd International Workshop on Global and Peer-to-Peer Computing on Large Scale Distributed Systems at the 2nd IEEE/ACM International Symposium on Cluster Computing and the Grid (CCGrid2002), 21-24 May, Berlin, Germany.

There are powerful normalising forces that get a wide range of tasks computed, if users are allowed to choose the complexity of tasks they want to compute (evolution@home is first to offer this option in global computing).
URL: http://doi.ieeecomputersociety.org/10.1109/CCGRID.2002.1017176

 

L2:     Loewe L (2002) "Global computing for bioinformatics.Briefings in Bioinformatics 3:377-388.

Reviews types of tasks and examples that can benefit from global computing in bioinformatics.
URL: http://bib.oxfordjournals.org/cgi/content/abstract/3/4/377

 

L1:     Loewe L and Scherer S (1997) "Mitochondrial Eve: The plot thickens.Trends in Ecology & Evolution 12:422-423.

Explores how archaeological data could be used to make inferences on mutation rates. Superseeded by newer work (under revision). 
URL: http://dx.doi.org/10.1016/S0169-5347(97)01204-4

 

Non-Refereed Publications

L9n:     Loewe L and Hill WG (2010) “Preface: Mutations and Brian Charlesworth.Philosophical Transactions of the Royal Society B 365:1151-1151.

Dedication of a themed issue on the population genetics of mutations to Brian Charlesworth on the occasion of his 65th birthday for his many contributions.
URL: http://rstb.royalsocietypublishing.org/content/365/1544/1151

 

L8n:     Loewe L and Viglas S (2010) “SQL vs NoSQL for simulation data management.” http://forum.idea.ed.ac.uk/ ; iDEA contribution; poster presented at “idea Lab lunch” 23 Feb 2010, School of Informatics, Uni Edinburgh.

Explores approaches for building extremely scalable simulation results databases, as needed for the analysis of very complex computational models.
URL: http://forum.idea.ed.ac.uk/idea/sql-vs-nosql-simulation-data-management

 

L7n:     Loewe L, Moodie S, and Hillston J (2009) “Technical Report: Defining a textual representation for SBGN Process Diagrams and translating it to Bio-PEPA for quantitative analysis of the MAPK signal transduction cascade.” Technical Report EDI-INF-RR-1334, School of Informatics, Uni Edinburgh.

Defines a textual representation for the systems biology graphical notation process diagrams and explains how this can be augmented by quantitative information to facilitate automated simulations.
URL: https://www.inf.ed.ac.uk/publications/report/1334.html

 

L6n:     Loewe L and Hillston J (2008) “Computational models in systems biology.” Invited meeting report. Genome Biology 9:328 (3 pages).

URL: http://genomebiology.com/2008/9/12/328

 

L5n:     Loewe L (2008) “Designing a Front-End for Bio-PEPA.” In: Gilmore S, editor. 7th Workshop on Process Algebra and Stochastically Timed Activities, 30-31 July 2008, Edinburgh (5 pages).

A design prototype for a biologist-friendly model implementation language is presented.
URL: http://pastaworkshop.org/proceedings/loewe-pasta2008.pdf

 

L4n:     Loewe L (2008) "Evolution@home: The first global computing system for evolutionary biology." invited chapter in the book "Distributed & Grid Computing - Science Made Transparent for Everyone. Principles, Applications and Supporting Communities" ed.: M. Weber, Rechenkraft.net.

 

L3n:     Loewe L (2008) “Negative Selection.” Nature Education 1(1),  Short introduction as invited by the editors of the “Evolutionary Genetics” section of the new “Nature Education” initiative

URL: http://www.nature.com/scitable/topicpage/Negative-Selection-1136

 

L2n:     Loewe L (2008) “Genetic Mutation.” Nature Education 1(1),  Short introduction as invited by the editors of the “Evolutionary Genetics” section of the new “Nature Education” initiative

URL: http://www.nature.com/scitable/topicpage/Genetic-Mutation-1127

 

L1n:     Loewe L (2006) “Population Genetics Group Meeting 2006.” Meeting report, Genetics Society News, Issue 57, pp. 22-25.

URL: http://www.genetics.org.uk/files/pdf/Genetics%20soc%20issue%2057.pdf   


Technical Reports and Other Publications

Loewe L, Keel SA, Ehlert K, Engbretson T, Goldfinger J, Scheuer K, and Flores-Lorka I (2015) "User manual for Evolvix 0.3.1." evolvix.org.  

URL: http://evolvix.org/download 


Loewe L (2015) "Evosysbio in 10 Slides." Figshare.com.

URL: http://figshare.com/articles/EvoSysBio_in_10_Slides/1427128

 

Loewe L and Keel SA (2014) "BEST Names for Semantic Units to Support Reproducible Modeling." (Contributed to "reproducibility@XSEDE" workshop, 4 pages, 2014-07-14, XSEDE14 Annual Conference, Atlanta, GA, USA.)

URL: https://www.xsede.org/documents/659353/703287/xsede14_loewe.pdf

 

James D, Wilkins-Diehr N, Stodden V, Colbry D, Rosales C, Fahey M, Shi J, Silva RF, Lee K, Roskies R, Loewe L, et al. [44 additional authors] (2014) "Standing Together for Reproducibility in Large-Scale Computing: Report on reproducibility@XSEDE." arXiv:1412.5557 [cs.DC].

URL: http://arxiv.org/abs/1412.5557  

 

Ehlert K and Loewe L (2013) "Lazy Updating increases the speed of stochastic simulations" Arxiv Quantitative Biology-Quantitative Methods, arXiv:1310.2068 [q-bio.QM] (preprint server).

URL: http://arxiv.org/abs/1310.2068