Simulation of molecular and evolutionary processes and programming language architecture for evolutionary systems biology.
- Wisconsin Institute for Discovery Room 3164, 330 N. Orchard Street
- Dr. rer. nat., TU Munich, Germany (2002), Postdoctoral Research: University of Edinburgh
- Medical Genetics
- Lab Website
- Research Interests
- Developing a stable, user-friendly programming language compiler for reproducible biodata analyses and general modeling in biology while building in-depth models for bioresearch in order to enable a mechanistic evolutionary systems biology integration of molecular systems biology models and population genetics for studying distributions of mutational effects
- Research Fields
- Computational, Systems & Synthetic Biology, Evolutionary & Population Genetics
- Jugend Forscht (similar to US Science Talent Search), extensive, self-directed research on Miller-Urey chemical evolution experiments, supported by several departments from different disciplines at the University of Erlangen, Germany; 5 competitions, 1987-1991.
- Biology MSc-equiv., focus on molecular aspects, experiments, University of Konstanz, Germany, 1995.
- rer. nat., Microbiology, Muller’s ratchet, evolution@home, Technical University of Munich, Germany, 2002.
- Postdoc in theoretical population genetics, University of Edinburgh, UK, 2003-2006.
- Lecturer in Evolutionary Genetics (sabbatical replacement), University of Edinburgh, UK
- Postdoc in process algebra modelling and quantitative analysis, focus on molecular systems biology, CSBE, Laboratory for Foundations of Computer Science, University of Edinburgh, UK, 2007-2010.
Nothing in biology makes sense except when properly quantified in the light of evolution.
From antibiotics resistance evolution and cancer to species extinction, evolution governs many challenges we face today; finding ways forward often requires causal insights from mechanistic models.
The Loewe Lab aims to improve the quality of diverse biological models by quantifying evolution with increasing precision. This inspired the PI to estimate the strength of selection in population genetics models from DNA sequence analyses and mutation accumulation experiments, approaches that struggle to quantify many types of mutational effects. Thus, Loewe investigates how to analyze molecular systems biology models from a population genetics view. He defined a framework for mechanistic evolutionary systems biology, which facilitates exploring mechanistic fitness landscapes by the versatile composition and analysis of complex biological simulation models.
To meet these challenging modeling demands, Loewe initiated the development of Evolvix, a modeling language he is designing to simplify mathematically accurate descriptions of concurrent systems that change over time. Such systems are often studied in biology, from biochemical reaction networks to evolving ecological webs. He develops a programming language architecture that integrates his 20+ years of experience in computational biology, in order to make Evolvix as user-friendly and as stable as possible. This work has inspired searching across disciplines for the best abstractions available for assisting biologists in navigating the complexity and diversity of biological systems. The Loewe Lab implemented a prototype of Evolvix that is currently used in the evolutionary systems biology modeling introduction course, which he developed at UW-Madison (Genetics 546).
Work with this prototype and in-depth usability reviews convinced Loewe that biology needs a dedicated general-purpose programming language designed by biologists for biologists. He develops formalisms and concepts for extending Evolvix accordingly without compromising its user-friendliness, which required a new approach to designing programming language architecture. As simulating evolution can quickly challenge any big computer, he is integrating Evolvix with evolution@home, the first globally distributed computing system for evolutionary biology that he started in 2001.
To keep Evolvix development relevant for working biologists, the in silico Loewe Lab also engages with a broad range of in-depth biological research to provide opportunities for testing on real-world problems. Such work includes building relevant Evolvix simulation models and the biodata science required for curating realistic model parameters. Research in his lab has investigated circadian clocks in flies, cholesterol biosynthesis, how selection shapes genomes, growing cancer cells, stochasticity in the evolution of cooperative behavior in game theory, potential genetic causes for species extinction, the evolution of antibiotics resistance, and more.
In-depth research with these models has also led to rich interactions with related theories for modeling, inspiring abstract aspects of compiler construction and contributing to the modeling framework developed for Evolvix. It also resulted in new perspectives on reproducibility, biosystems curation, biodata science, statistical logic, and the formal computing tools that are required for enabling biologists of the future to more efficiently learn from past results, positive or negative, in order to better build on today’s biological data and results (see FlyClockbase, 2017).
The ability to build efficiently and reproducibly on existing computational results is key to solving many biological problems with a practical impact.
More details can be found on the
- Loewe Lab website, the
- Evolvix website at http://evolvix.org , and the
- Evolutionary Systems Biology website at http://evolutionarysystemsbiology.org.
A Programming Language for Biology
Loewe initiated and continues to work on a programming language architecture for enabling the efficient development of a long-term backwards compatible, user-friendly, general-purpose programming language designed by biologists for biologists. While the Evolvix website at http://evolvix.org offers a very early prototype implementation (free download) and some other results, most of the design material is yet to be published. Evolvix architecture is extended and refined in the Loewe Lab through a broad array of conventional and unconventional methods, none of which work without contributions from numerous Evolvix Thinkers. Particularly powerful secret weapons of high-tech engineering and advanced science constantly used in the Loewe Lab include white-board walls, and most importantly: paper in many shapes and sizes.
The work on Evolvix has been motivated by a substantial long-term need for a more integrated error management handling of many different types of problems in computational biology. Many of these problems easily arise in complex mechanistic and probabilistic analyses that are necessary for the computation of fitness causality networks in mechanistic evolutionary systems biology (EvoSysBio). The EvoSysBio website at http://evolutionarysystemsbiology.org provides a high-level overview and Loewe has been at the forefront of defining EvoSysBio with an important framework definition in 2009 that was redefined in 2016. For a TL;DR version of these thorough papers, see EvoSysBio in 10 slides.
Anuual EvoSysBio Meetings
Loewe organized EvoSysBio meetings in various forms and maintains the most complete curated list of past meetings in evolutionary systems biology. Entries are added as new meetings become known.
Interested in the Loewe Lab?
Interested in working on modeling, biosystems curation, or reproducibility in the Loewe Lab? Ready for in silico biology, but can’t program? Not scared about improving names for concepts or exploring semantics in-depth? Interactive writing support sounds cool? If you have the tenacity to work and learn in the heat where concepts for tomorrow are being forged, specify what you look for, what you bring to the lab, and why the lab is a great fit. Argue well and you might earn an interview; but be warned, the Lab builds biodata science tools for the professional biosystems curators of tomorrow. To speed them up, some steps today need slow-motion analysis or very advanced programming skills. Breaking new ground is not fast. So, most computational biology is more fun elsewhere, your industry experience in C++, CMake, node.js etc., deserves what the Lab can’t pay, and you need to get the MOs in the Lab’s (2017) BESTnames paper to program here.
Yet, this unusual Lab thrives on synergies between its members’ special skills for its own ‘Mission Impossible’. Do your hidden talents fit now? Impossible to predict. Apply with all details you want to share, so the Lab can reply as opportunities appear. Some may require that you are self-funded, or can volunteer time, or enroll in a special course, or find a training grant (see below), or that the Lab has funds. An easy way to learn more about the type of modeling work done in the Lab is to attend the evolutionary systems biology modeling introduction course, (Genetics 546).
- Evolutionary systems biology modeling introduction course (Genetics 546)
Syllabus (currently each Fall).
- In-depth Research Seminar on Foundational Aspects in Computational Biology
Syllabus (offered only as the need arises).
The Loewe Lab regularly participates at these events:
- Darwin Day organized by the James F Crow Institute for the Study of Evolution
- Wisconsin Science Festival
If you are interested in organizing a special outreach event that involves modeling some aspects in biology or other aspects of our work, do not hesitate to contact the LoeweLab.
For extending outreach activities, the Loewe Lab is looking for a middle-school or high-school teacher interested in the (paid) summer work of developing the materials for more efficiently teaching high-school students about modeling by using the Evolvix platform developed in the lab.
- Laboratory of Genetics
- Wisconsin Institute for Discovery
- School of Medicine and Public Health (SMPH)
- F. Crow Institute for Study of Evolution
- Quantitative Biology Initiative (QBI)
- University Library Committee
PhD students in the following training programs can join the lab more easily than others:
- Training Program: Genetics Training Program (GTP)
- Training Program: Genomic Sciences Training Program (GSTP)
- Training Program: Computation and Informatics in Biology and Medicine (CIBM)
- Training Program: Microbiology Doctoral Training Program (MDTP)
NSF Career Award (2012) Modeling made easy: Extending systems biology modeling approaches to genetics and ecology.
Search Pubmed for more publications by Laurence Loewe:
McLoone B, Fan W-T L, Pham A, Smead R, and Loewe L (2018) “Stochasticity, Selection, and the Evolution of Cooperation in a Two-Level Moran Model of the Snowdrift Game”, Complexity, in press, Article ID 9836150 – Link to DOI
Warren, Wesley C, García-Pérez R, Xu S, Lampert KP, Chalopin D, Stöck M, Loewe L, Lu Y, Kuderna L, Minx P, Montague MJ, Tomlinson C, Hillier LW, Murphy DN, Wang J, Wang Z, Garcia CM, Thomas GCW, Volff J-N, Farias F, Aken B, Walter RB, Pruitt KD, Marques-Bonet T, Hahn MW, Kneitz S, Lynch L & Schartl M (2018) “Clonal polymorphism and high heterozygosity in the celibate genome of the Amazon molly”, Nature Ecology & Evolution (online advance publication) – Link to DOI – Press coverage: BBC
Scheuer KS, Hanlon B, Dresel JW, Nolan ED, Davis JC, Loewe L (2017) “FlyClockbase: Importance of Biosystems Curation for Analyzing Variability in Circadian Clock of Drosophila melanogaster by Integrating Time Series from 25 Years of Research”
[book-length discussion of circadian clock biodata science that is currently being transformed into a series of reports for a special issue] – Link to BioRxiv DOI
Loewe L, Scheuer KS, Keel SA, Vyas V, Liblit B, Hanlon B, Ferris MC , Yin J, Dutra I, Pietsch A, Javid CG, Moog CL, Meyer J, Dresel J, McLoone B, Loberger S, Movaghar A, Gilchrist-Scott M, Sabri Y, Sescleifer D, Pereda-Zorrilla I, Zietlow A, Smith R, Pietenpol S, Goldfinger J, Atzen SL, Freiberg E, Waters NP, Nusbaum C, Nolan E, Hotz A, Kliman RM, Mentewab A, Fregien N, Loewe M (2017) “Evolvix BEST Names for semantic reproducibility across code2brain interfaces” Ann. New York Acad. Sci. 1387:124-144 – Link to DOI for updates see http://evolvix.org/naming and more on the POSTsystem
Loewe L (2016) “Systems in Evolutionary Systems Biology”, pp. 297-318, vol. 4, in Encyclopedia of Evolutionary Biology, ed.: Richard M. Kliman, Oxford, UK, Academic Press. doi:10.1016/B978-0-12-800049-6.00184-0 – Link to PDF
James D, et al. (2014) “Standing Together for Reproducibility in Large-Scale Computing: Report on reproducibility@XSEDE” – http://arxiv.org/abs/1412.5557
Loewe L (2015) “EvoSysBio in 10 Slides”, Figshare.com – Link to DOI
Loewe L (2015) “EvoSysBio LIFTs: Microbes and Antibiotics”, Figshare.com – Link to DOI
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 – Links to DOI
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, 17 pages. PMCID: PMC3496668 – Link to DOI
Modrzynska K, Creasey A, Loewe L, Cezard T, Martinelli A, Borges S, Cravo P, Blaxter M, CarterR, and Hunt P (2012) “Genome-wide re-sequencing defines mutations of complex chloroquine resistance in malaria”. BMC Genomics 13:106, 16 pages – Link to DOI
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”, Lecture Notes in Computer Science LNCS vol. 6575, pages 13-38 – Link to DOI
Loewe L and Hill, WG (2010) “Introduction: The population genetics of mutations: good, bad and indifferent”. Philosophical Transactions of the Royal Society Series B
vol. 365:1153-1167 – Link to DOI
Akman OE, Guerriero M-L, Loewe L and Troein C (2010) “Complementary approaches to understanding the plant circadian clock”, Electronic Proceedings in Theoretical Computer Science (EPTCS) 19:1–19 – Link to DOI
Loewe L, Moodie S and Hillston J (2009) “Quantifying the implicit process flow abstraction in SBGN-PD diagrams with Bio-PEPA”, Electronic Proceedings in Theoretical Computer Science (EPTCS) 6:93-107 – Link to DOI – Builds a compiler to build a bridge from visual model construction to automated simulations.
Loewe L (2009) “A framework for evolutionary systems biology“. BMC Systems Biology 3:27, 34 pages, – Link to DOI
Loewe L and Hillston J (2008) “The distribution of mutational effects on fitness in a simple circadian clock“, CMSB08, Lecture Notes in Bioinformatics 5307:156-175 – Link to DOI
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 – Link to DOI
Loewe L (2007) “Evolution@home: observations on participant choice, work unit variation and low-effort global computing“. Softw. Pract. & Exp. 37:1289-1318 – Link to DOI
Loewe L and Charlesworth B (2007) “Background selection in single genes may explain patterns of codon bias“. Genetics 175:1381-1393 – Link to DOI
Loewe L and Charlesworth B (2006) “Inferring the distribution of mutational effects on fitness in Drosophila“. Biology Letters 2:426-430 – Link to DOI
Loewe L (2006) “Quantifying the genomic decay paradox due to Muller’s ratchet in human mitochondrial DNA“. Genetical Research 87:133-159 – Link to DOI
Loewe L, Charlesworth B, Bartolomé C and Nöel V (2006) “Estimating selection on non-synonymous mutations“. Genetics 172:1079-1092 – Link to DOI
Loewe L, Textor V and Scherer S (2003) “High deleterious genomic mutation rate in stationary phase of Escherichia coli“. Science 302:1558-1560 – Link to DOI
Loewe L (2002) “Global computing for bioinformatics“.
Briefings in Bioinformatics 3:377-388 – Link to DOI
Naming is hard. In fact it is one of the hardest problems in biology, computer science, math, etc., and also the most costly activity in the Loewe Lab so far. Hence the lab’s research on naming. For example, we defined the data type ‘BioBinary’. In a funny twist of fate, the name of the PI (‘Loewe’) is rarely pronounced correctly. The PI doesn’t care, as long as the semantics is clear: ‘Loewe’ is German for ‘Lion’.