how hpc is boosting cutting-edge biology

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How HPC is Boosting Cutting Edge Biology !

How HPC is Boosting Cutting-Edge Biology

High!Performance!Computing!(HPC)!is!adding!momentum!to!the!evolution!of!biological!science!and!a!revolution!in!our!understanding!of!how!biological!systems!function!–!as!pioneering!research!at!UCL!is!clearly!demonstrating.!!To!drive!their!work!forward,!Dr!Chris!Barnes!and!his!Computational!Systems!and!Synthetic!Biology!Group!make!extensive!use!of!HPC,!especially!the!Emerald!supercomputer!developed!by!UCL!with!Bristol,!Oxford!and!Southampton!Universities!and!funded!by!the!Engineering!and!Physical!Sciences!Research!Council!(EPSRC).!!The!group!is!at!the!leading!edge!of!the!fastKdeveloping!field!of!quantitative!biology,!a!discipline!that!uses!measurable!data!and!mathematical!modelling!to!reveal!the!secrets!of!the!living!world!–!with!Emerald’s!sheer!computational!power!and!speed!helping!to!generate!insights!that!could!lead!to!dramatic!advances!in!spheres!such!as!drug!development!and!gene!therapy.!!

Biology Breaks Out Biology!is!one!of!the!great!natural!sciences.!Traditionally,!its!main!focus!has!been!on!identifying!and!characterising!the!different!elements!within!biological!systems.!But!how!do!these!elements!actually!combine!and!work!together?!This!key!gap!in!understanding!helped!to!trigger!the!comparatively!recent!emergence!of!quantitative!biology,!which!strives!to:!

• !Establish!firm!mathematical!and!physical!foundations!enabling!biological!science!to!secure!new!insights!and!break!into!new!areas.!

• Harness!a!comprehensive!array!of!computational,!mathematical!and!statistical!tools!and!techniques!to!make!this!possible.!

!“My!group!supplements!experimental!methods!with!mathematical!modelling!and!statistical!analysis,”!Chris!Barnes!explains.!“We!then!apply!these!tools!to!biological!systems!and!synthetic!biology!–!an!emerging!discipline!specialising!in!the!design!and!construction!of!artificial!biological!systems!and!the!redesign!of!existing!ones,!with!potential!uses!not!just!in!medicine!and!healthcare!but!also!in!areas!such!as!energy!and!the!environment.”!A!key!element!in!this!work,!which!is!underpinned!by!UK!Research!Council!funding!and!support!from!the!Wellcome!Trust,!involves!building!mathematical!models!of!biological!systems!to!show!how!they!

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function!and!might!be!improved.!“We!use!models!to!make!predictions!that!we!then!test!through!physical!experiments,!which!in!turn!generate!results!that!we!feed!back!into!the!models,”!says!Dr!Barnes.!“It’s!a!process!where!modelling!and!experimentation!are!continually!reinforcing!one!another.”!!!A!key!element!in!this!work,!which!is!underpinned!by!UK!Research!Council!funding!and!support!from!

the!Wellcome!Trust,!involves!building!mathematical!models!of!biological!systems!to!show!how!they!function!and!might!be!improved.!“We!use!models!to!make!predictions!that!we!then!test!through!physical!experiments,!which!in!turn!generate!results!that!we!feed!back!into!the!models,”!says!Dr!Barnes.!“It’s!a!process!where!modelling!and!experimentation!are!continually!reinforcing!one!another.”!!

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Emerald Shines Vital Light on Key Questions In!a!field!where!computational!tools!naturally!play!a!pivotal!role,!HPC!has!delivered!a!step!change!in!capabilities!enabling!the!team!to!carry!out!increasingly!complex!and!sophisticated!modelling!with!phenomenal!speed!and!accuracy.!In!this!context,!Emerald,!located!at!Rutherford!Appleton!Laboratory!in!Oxfordshire!and!the!UK’s!most!powerful!supercomputer!based!on!Graphics!Processing!Units!(GPUs),!has!been!a!gameKchanger.!!

!!!“We!first!harnessed!Emerald!in!summer!2012!as!one!of!its!very!first!pilot!users,”!Chris!Barnes!confirms.!“Since!then,!Emerald!has!become!absolutely!integral!to!the!challenging!work!we!do!using!complicated!nonKlinear!models!to!investigate!different!types!of!biological!processes!and!to!improve!understanding!of!their!complexities.”!!

“Some&of&our&projects&simply&couldn’t&and&wouldn’t&have&

happened&without&the&computing&power&that&Emerald&provides.”&

&=&&Dr&Chris&Barnes,&Lecturer&in&

Systems&Biology!

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As!the!following!recent!examples!show,!this!cuttingKedge!84Knode!cluster!is!adding!real!value!to!the!groundKbreaking!research!being!pursued!by!the!Barnes!group:!

• DNA!repair!and!mutation:!The!DNA!strands!in!living!cells!are!crucial!carriers!of!genetic!information,!but!they!can!be!damaged!by!a!range!of!sources!originating!both!inside!and!outside!the!cell.!Complex!repair!systems!have!evolved!over!millions!of!years,!varying!according!to!factors!such!as!the!nature!of!the!damage!and!the!stage!in!the!cell’s!life!cycle!at!which!it!occurs.!In!some!cases,!though,!the!repair!process!can!misfire!and!result!in!mutations!–!some!of!which,!like!cancer,!can!have!serious!health!implications.“We’ve!recently!used!Emerald!to!help!us!apply!modelling!and!statistical!methods!to!genomic!and!experimental!data,!to!shed!light!on!different!DNA!repair!and!mutation!mechanisms,”!says!Dr!Mae!Woods,!an!applied!mathematician!in!the!group.!“For!example,!Chris!Barnes!and!I!have!made!extensive!use!of!the!facility!to!develop!a!computational!model!of!DNA!repair.”!

• Engineering!bacteria:!The!engineering!of!soKcalled!‘commensal’!bacteria!(which!can!exist!inside!other!organisms!without!harming!them)!has!exciting!potential!in!terms!of!creating!new!forms!of!therapy!and!revolutionary!tools!for!disease!diagnosis.!Such!bacteria,!however,!need!to!be!capable!of!functioning!in!wideKranging!and!everKchanging!temperature,!pH!and!other!conditions!–!which!makes!it!vital!to!be!able!to!predict!which!designs!of!bacteria!will!be!the!most!robust.!

!!“With!Emerald’s!help,!we’ve!developed!and!tested!design!methods!that!allow!the!selection!of!the!genetic!networks!incorporated!into!engineered!bacteria!to!be!based!on!the!networks’!robustness!to!external!noise”,!says!PhD!student!Miriam!Leon.!!

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Biology Benefits By!adding!an!extra!component!to!the!group’s!toolkit,!Emerald!is!certainly!meeting!its!goal!of!delivering!superKfast!processing!that!accelerates!research!and!solves!problems!quicker.!“Some!of!our!projects!simply!couldn’t!and!wouldn’t!have!happened!without!the!computing!power!that!Emerald!provides,”!Chris!Barnes!affirms!unequivocally.!!“Take!our!recent!research!into!transcriptional!oscillators!as!part!of!our!work!on!bacteria.!Some!of!the!simulations!that!we!completed!in!a!few!hours!using!Emerald!would!have!taken!up!to!a!week!running!on!single!GPU!cards,!and!generating!the!results!required!hundreds!of!runs.!But!just!as!important!as!raw!computing!power!is!the!fact!that!Emerald!is!so!accessible,!easy!to!use!and!underpinned!by!such!excellent!technical!support!–!all!of!which!makes!a!massive!difference!to!our!ability!to!meet!the!challenges!presented!by!this!fascinating!and!increasingly!influential!field!of!biology.”!!

Contacts Dr!Chris!Barnes–!Lecturer!in!Systems!Biology,!UCL,!E:[email protected]!Dr!Mae!Woods!–!Research!Associate!in!Mathematical!Modelling,!UCL,!E:[email protected]!Miriam!Leon!–!PhD!Student,!Department!of!Cell!&!Departmental!Biology,!UCL,!E:[email protected]!!!!!!!!!!!

Discover)more)online)!

http://www.ses.ac.uk/2016/04/07/hpcKboostingKcuttingKedgeKbiology/!!http://www.ses.ac.uk!

!@SES_Consortium!

“We’ve&used&Emerald&to&help&us&apply&modelling&and&statistical&methods&to&genomic&and&

experimental&data,&to&shed&light&on&different&DNA&repair&and&mutation&mechanisms.”&&

&=&Dr&Mae&Woods,&Research&Associate&in&

Mathematical&Modelling!

how hpc is boosting cutting-edge biology

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