Sequencing Technology 2012 – Jeff Schloss

WE’RE GOING TO NOW MOVE TO AN UPDATE THAT’S ACTUALLY BEEN DELAYED FOR A COUPLE COUNCIL MEETINGS BY JEFF FLOSS, I KNOW THERE’S SIGNIFICANT INTEREST IN HEARING ABOUT THE SEQUENCING TECHNOLOGY PROGRAM WHICH HAS BEEN WIELDLY SUCCESSFUL AND WHERE IT’S GOING AND SO, JEFF SCHLOTZ DIRECTING THAT PROGRAM FOR MANY YEARS WILL GIVE US AN UPDATE AND JEFF, JUST 1 SECOND ISSUES HAVE YOU BLUE FOLDERS AT YOUR SEATS THAT CONTAINS THE CONFLICT OF INTEREST DOCUMENT MAKE SURE TO SIGN IT AND WE’LL COLLECT IT AT THE LUNCH BREAK >> ANYBODY KNOW WHAT BUTTON I HAVE TO PUSH? >> YOU’RE ON A LAPTOP? >> TO GET IT TO LOOK AT MY LAB TOP IS >> OKAY, IT’S INTERESTING TO HAVE THESE 2 BACK?TO?BACK SO I WILL TALK ABOUT THE TECHNOLOGY DEVELOPMENT FOR DNA SEQUENCING, I WON’T GO QUITE AS FAR BACK AS KAREN DID BUT I’LL ONLY GO BACK TO THE END OF THE HUMAN GENOME PROJECT WHERE WE WERE IS >> ??THERE’S A LOT OF INTEREST FOR MANY REASONS, MEDICAL BUT ALSO WHAT’S GOING ON IN THE ENVIRONMENT, HOW DO THOSE MICROBIAL COMMUNITIES AFFECT OUR FOOD AND OTHER AGENCIES AT THE GOVERNMENT THAT ARE PARTICULARLY INTERESTED IN DETECTION TECHNOLOGIES THAT YOU SEQUENCING AND THERE’S A LOT OF RATIONAL TO DO SOME MORE AT THE TIME WHEN THE HUMAN GENOME PROJECT WAS FINISHED, THIS WAS SORT OF A CHAMPION SOMEONE, IT WAS A RESULT OF QUITE STUNNING TECHNICAL EVOLUTION AND IT WAS NOTICED THAD DURING THE TIME OF THE HUMAN GENOME PROJECT THE COST OF SEQUENCING DID DROP DRAMATICALLY AS A CONSEQUENCE OF COLLECTION IN IMPROVEMENTS AND ECONOMYS OF SCALE AND WHEN 1 LOOKED AT THE TREND, 1 COULD SEE THAT IT TOOK ABOUT 10 YEARS TO REDUCE COSTS BY TOURS OF THIS MAGNITUDE, THE ESTIMATES THAT IT COSTS SOMETHING ON THE ORDER OF 600 TO $700,000, THE SEQUENCE IN THE GENOME AND IF YOU HAD DONE IT AGAIN AT THE END WITH THE TECHNOLOGY THAT THE EXTENT TO WHICH DID HAD DONE IT AGAIN AT THE END OF THE HUMAN GENOME PROJECT IT WOULD ESTIMATED TO COST 50 MILLION DOLLAR TO SEQUENCE A HUMAN GENOME??YES? BUT 600 DID I SAY MILLION? 600 MILLION DOLLARS I SAID THOUSAND SORRY 600 MILLION IT SHOULD BE BIGGER THAN 50 MILLION YEAH, YEAH >> 600 TO 700 MILLION I’M SORRY >> SO THE ARREST OF THE 2 OPINIONED 5 BILLION WAS SEQUENCING OTHER GERONTOLOGYSTS DMOMS AND MAPPING AND ALL THAT?? >> YEAH YEAH >> TRYING TO FIGURE IT OUT >> RIGHT YEAH, YEAH RIGHT SO IN THE PLANNING PROCESS, THE PREVIOUS PLANNING PROCESS ISSUES THE 1 THAT WAS PUBLISH INDEED APRIL 2003, AS YOU ALL REMEMBER THIS WAS THE ICON FOR THAT PROGRAM AND THAT ACTUALLY AT THE FIRST BOOK?INS MEET CHICAGO WAS DECEMBER 2001, I THINK, IT’S THE DATE FI HAVE THE DATES RIGHT THIS NOTION OF SEQUENCING A GENOME FOR A THOUSAND DOLLARS WAS PROPOSED, I BELIEVE THAT’S THE FIRST TIME IT WAS

PROPOSED WHEN I HEARD IT AND ANYWAY AS PART OF THIS PLAN, WE DEFINED A SERIES OF QUANTUM LEAPS AND ALMOST FAR OFF WAS FICTIONAL, AND IF THEY COULD BE, IF YOU WOULD REVOLUTIONIZE BIOMEDICAL RESEARCH AND SO, AS A RESULT OF THAT, PLANNING PROCESS, WE DID LAUNCH A SET OF RFAs, WHERE WE STARTED IN 2004 AND SAID AT THE CURRENT TIME, THE COST OF A HIGH QUALITY DRAFT IS SOMEWHERE IN THE RANGE OF 10 TO 15 MILLION DOLLAR AND THE GOAL OF THIS INITIATIVE WAS TO REDUCE THAT COST ON HALF THE TIME SCALE, IN 2 ORDERS OF COST PRODUCTION IN 5 YEARS AND ANOTHER 2 ORDERS OF MAGNITUDE OF COST REDUCTION IN THE SUBSEQUENT 5 YEARS THAT WOULD TAKE YOU DOWN TOO A HUNDRED THOUSAND DOLLARS IN 5 YEARS AND A THOUSAND DOLLARS IN 10 YEARS SO THOSE WERE OUR GOALS AND INITIAL AWARDS WERE MADE IN 2004 I SHOULD ADD THAT WITHOUT A METRIC, THE COST REDUCTION IS MEANING LESS SO FOR A VERY, VERY, CHALLENGING TECHNOLOGY GOAL WAS TO PRODUCE A HIGH QUALITY DRAFT, NOT THE FINISHED SEQUENCE, OF THE 50 MILLION DOLLAR COST REPRESENTS BUT A HIGH QUALITY DRAFT SO WE WENT TO THE LOWER END, THE 10 MILLION AS OUR ESTIMATE THIS IS THE DRAFT OF THE MOUSE GENOME AND WE USE THAT BECAUSE THERE WERE METRICS IN THAT THE QUALITY AND CONDIGUITY AND SOT FORTH SO LET ME GRAB SOMETHING WE ISSUED RFAs FOR APPLICATIONS OVER THE YEAR, WE ALWAYS HAD R21 FEASIBILITY PROGECS AND RO?1 RESEARCH GRANTS AND AT VARIOUS TIME WEES ROLL INDEED SMALL BUSINESS GRANTS UNDER THE PROGRAM I SAY SHOULD SAY THAT AS KAREN MENTIONED ALL THE GRANTS ARE LISTED FOR ELSI ALL THE GRABTS ARE POSTED ON THIS WEB SITE, AND WE’VE MADE ROUGHLY 52 MILLION DOLLAR IN AWARDS FOR THE FIRST COMPONENT, THE HUNDRED THOUSAND DOLLARS GENOME BETWEEN 2004 AND 2010, THE LAST AWARDS WERE 0ED IN 2008 AND SO THAT’S 52 MILLION DOLLARS OF THAT COMMENNENT AND 125 MILLION IN TWEPMENT OF TECHNOLOGIES FOR THE THOUSAND DOLLAR GENOME IN 2000 SINCE 2004 AND THAT INCLUDES THE COMMITMENT OUT TO 2013 THAT HAVE COMMITMENTS THAT’S MOSTLY IN RO?1S AND R21S THE OVERALL WITHIN THAT, THE OVERALL INVESTED IN SMALL BUSINESS GRANTS IS ABOUT 11 MILLION DOLLARS THE AVERAGANNUAL COST IN THIS PROGRAM EXPENDITURE IN THIS PROGRAM HAS BEEN ABOUT 20 MILLION DOLLARS WITH THE LARGEST IN FYFISCAL YEAR 2005 AND 2006 IN ADDITION TO THOSE NUMBERS, I SHOULD SAY THAT ABOUT 13 MILLION DOLLAR IN STIMULUS AWARDS WERE MADE THE COPE OF THAT PROGRAM WAS A BIT BROADER THAN THE SCOPE OF THIS RFA SO WE’RE UP IN THE RANGE OF 190 MILLION DOLLARS OVER THE PERIOD OF TIME OF THIS PROGRAM AND WE FUNDED 45 ACADEMIC GROUPS IN IN TIME SOME OF THESE RECEIVE MULTIPLE AWARDS THEY MAY HAVE HAD A R1 OR RO?1 OR PROJECTS WITH DIFFERENT HANDS, ABOUT 45 ACADEMIC GROUPS AND 19 COMPANIES AND THE COMPANIES RANGE FROM START UPS TO MIDSIZE COMPANIES THAT ARE??SOME OF WHICH ARE VENDORS OF SEQUENCING TECHNOLOGIES TO QUITE LARGE COMPANIES INCLUDING GE AND IBM SO IT’S BEEN A VERY INTERESTING PROGRAM IN QUICK TERMS OF DIVERSITY, OF THE GRANTEES AND WE PRODUCED WELL OVER 300 PUBLICATIONS IN THE PROGRAM AND LARGE NUMBERS OF PATENTS WE’RE FINDING OUT MORE ABOUT THE LICENSING SO OVER THIS PERIOD OF A PROGRAM, WE MADE AWARDS IN A WIDE VARIETY??WE MADE A WIDE VARIETY OF KIND OF INVESTMENT FROM RELATIVELY NEAR TERM TO THE WAY THE HUMAN GENOME PROJECT WAS DONE TO MUCH MORE FUTURISTIC SOME OF THIS THE SCIENCE IS WELL UNDERSTOOD, BUT THERE WERE SIGNIFICANT ENGINEERING CHALLENGES AND OTHERS WE WERE REALLY MOVING INTO NEW AREAS OF SCIENCE WHERE WE REALLY DEPARTMENT UNDERSTAND PHYSICS EMPLOY AND THAT’S BEEN 1 OF THE EXCITING COMPONENTS OF THIS PROGRAM AND RISK TAKING THESE ARE JUST TITLES OF THE KINDS OF GRANTS THAT WERE FUNDED AND RANGING FROM POLLENATING SEQUENCING AND SIPGHT SIS WE’LL TALK ABOUT IN A MINUTE AND ALL THE WAY OUT TO

VARIOUS NUMBER OF DIFFERENT MOLECULE METHODS, THERE’S A DIVERSITY OF METHODS, WE’VE TRIED LOTTINGS OF DIFFERENT THINGS OR CONTINUING TO TRY LOTS OF DIFFERENT THINGS THAT INVOLVE MASS SPECTROMETRY AND FORCED SPECROSCOP SCHECHARGED BASE SEQUENCING MICROFLUIDICS AND SO FORTH IT’S BEEN A QUITE BROAD PROGRAM I’M NOT GOING TO TRY TO TEACH YOU HOW TO DO SEQUENCING BUT I NEED TO TALK I LITTLE BIT ABOUT HOW THE TECHNOLOGIES WORK AND GIVE YOU AWE CONTRAST FROM WHERE WE ARE NOW TO WHERE WE’RE TRYING TO GO SO THE CURRENT SORT OF THE STATE?OF?THE?ART SEQUENCING TECHNOLOGIES INSOLVE SEQUENCING BY SIPGHT SIS OR SEQUENCING LIGATION MANY OF THEM ARE ENSEMBLE METHODS AT LEAST SEQUENCING YOU’RE FEATURING A LARGE CLUSTER OF MOLECULES SOME OF THEM ARE SINGLE MOLECULE AND MOST OF THEM INVOLVE DETECTION, OPTICAL DETECTION USING FLUORESCENCE AND CHEMICAL LUMINESCE ENSEL LET ME WALK YOU THROUGH QUICKLY, I WILL TRY TO DO THIS QUICKLY BUT NOT TOO RUSHED, A NUMBER OF THESE IN ORDER TO MAKE THESE ENCOMBLES OF MOLECULES WE’LL START WITH GENOMIC DNA PUT SOME LITTLE TAG O SINGLE THEM SO WE CAN HANDLE THE ENDS OF THOSE FRAGMENTS OF GENOMIC DNA AND SO THAT FROM 1 PIECE, FROM 1 FRAGMENT OF GENOMIC DNA WILL MAKE A WHOLE BUNCH OF COPIES AND THIS SLIDE REPRESENTS 1 WAY TO DO THAT YOU MIX LITTLE BEADS THAT CAN CAPTURE THOSE POLARIZED MOLECULES IN REAGENTS AND THE QUESTION NATIONAL LIBRARY OF MEDICINIC DNA PRAYING MENTORSHIP SKILLS AND YOU PUT THAT ON A VORTEX AND YOU MAKE AN OIL AND WATER EMULSION SO HAVE YOU DROPLETS OF AQUESTIONUS SOLUTION THAT HAVE ALL THE REAGENTS AND BEADS AND DNA SURROUNDED BY OIL SO THIS IS A LARGE NUMBER OF TEST TUBES AND INSIDE EACH OF THOSE LITTLE TEST TUBES AMPLIFICATION OCCURS AND WE END UP WITH A DNA MOLECULE AND A BEAD THAT HAS LOTS OF DNMOLECULES ALL OF WHICH ORIGINATED IN THE SAME GENOMIC FRAGINENT AND 1 OF THE THEMES HERE IS THAT THE WORK FLOW IMPROVED A LOT AND THIS IS 1 OF THE REASONS THAT WE’VE BEEN ABLE TO PRODUCE THE COST AND THE THROUGH PUT INCREASES WE HAVE SO YOU GENERATE LITTLE FEATURES IN THIS CASE, PIECES THAT HAVE LARGE NUMBERS OF COPIES AND TEMPLATES YOU COULD USE FOR SEQUENCING REACTION AND WE SKIPPED THE CLONING AND COLONY PICKING AND THAT’S VERY LABORIOUS COMPONENT THAT WAS NECESSARY DURING THE SANGER SEQUENCING ERA OF HUMAN GENOMIC PRODUCTION AND YOU ALSO GET RID OF, YOU LOSE A NUMBER OF BIASES IN THE KIND??IN THE DNA MOLECULES YOU COLLECT THIS IS AN EXAMPLE OF OF ANOTHER WAY TO MAKE THOSE CLUSTER WITH MOLECULES WHERE INTED OF DOING IT ON BEADS YOU DO IT ON A SURFACE WITH MANY OF THOSE CLUSTERS BUILT ON THE SURFACE THIS IS A DIAGRAM OF WHAT SEQUENCING BY SYNTHESIS LOOKS LIKE SO ON THE LEFT WILL BE A DIAGRAM OF WHAT’S GOING ON, SORT OF CHEMICALLY, WHERE WE’RE WE’RE GOING TO SEE IS EACH OF THOSE BLUE DOT SYSTEM A FEATURE THAT HAS A CLUSTER OF DNA MOLECULES EACH OF WHICH ORIGINATE FRIDAY A I THINKLE DENATIONAL LIBRARY OF MEDICINIC DNA FRAG METROPOLITAN AND WE’LL BUILD 1 AT A TIME ANOTHER NUCLEOTIDE, ANOTHER NUCLEOTIDES LE TIDE AND ON THE RIGHT HAND SIDE IS WHAT THE MICROSCOPE WOULD SEE LOOKING AT THAT CHIP SURFACE SO IT’S GOING TO BUILD UP AND YOU DO CHEMISTRY AND IMAGE AND DO CHEMISTRY AND IMAGE YOU CAN ACHIEVE THAT BY USING POLYMERASE TO GROW THAT CHAIN AND THAT’S WHAT SOME OF THE SYSTEMS DO AND YOU CAN ALSO ACHIEVE IT BY DOING OLIGONUCLEOTIDE I’LL TALK ABOUT A NUMBER OF INDIVIDUAL TECHNOLOGIES THAT ARE COMMERCIAL PRODUCTS AND I’M NOT ENDORSING OF ANY OF THOSE BUT IT’S IMPORTANT TO HAVE THE CONTEXT TO MENTION THESE SYSTEMS AND THE SYSTEMS IN DOING SO I’LL MENTION THE PEOPLE THAT DEVELOPED THEM SO WHAT YOU GET IS IMAGES THAT LOOK LIKE THAT AND THEY’RE STACKED UP ON EACH OTHER AND YOU CAN SEE IF CAN YOU MAKE THE DOTS SMALLER, AND CLOSER TOGETHER AND MORE UNIFORM, THERE’S LOTS OF ROOM TO INCREASE THROUGH PUT AND THAT’S SOME OF THE WHAT’S BEEN GOING ON OVER THE LAST SEVERAL YEARS TO PRODUCE THE REMARKABLE IMPROVEMENTS IN THROUGH PUT AND QUALITY AND SO FORTH THAT HAVE BEEN ACHIEVED SO AGAIN TO STRESS THE WORK FLOW CHANGE, WE WEPT FROM DOING RUNS WHERE WE HAD LARGE

SETS OF ROBOTS TO HANDLE ALL THESE SAMPLES INDIVIDUALLY AND HUNDRED SAMPLES ANALYZED PER RUN TO BEING ABLE TO PREPARE THE LIBRARIES WITHOUT CLONING IN A TEST TUBE AND THEN DIDDING RUNS THAT HAVE MILLIONS OF, HUNDREDS OF MILLIONS OF SAMPLES BEING SEQUENCED AT A TIME NOW THE DURATION OF THE RUN IS DIFFERENT AND I DON’T WANT TO INDICATE THAT IT’S EASY TO MAKE THESE LIBRARIES BUT IT IS A LOT EASIER [CHECK] OVER A PERIOD OF YEARS, A SERIES OF INSTRUMENTS HAVE BEEN COMMERCIALIZED, THE DATES OF COMMERCIALIDESSATION OF THESE INSTRUMENTS AND THE ASTERISKS ARE THE GRANTEES SO WE HAVE N HGRI HAS HAD A ROLE IN CONTRIBUTING TO THESE TECHNOLOGIES FOR MOST OF THE CURRENT SYSTEM DIFFERENT KINDS OF INVESTMENTS SO BY THE TIME WE INVEST INDEED THE 454 SYSTEM, THEY WERE ALREADY ON A COMMERCIALIZATION PATH THEY HAD A GRANT FROM US FOR SCALING TO SCALE UP FASTER AND IMPROVE FASTER SO WE ORIGINALLY FUNDED AS A NEW INVESTIGATOR AWARD TO SEE PI AND ACADEMIC INSTITUTION, WE DEVELOP THE CONCEPTS BEHIND THE SINGLE MOLECULE SEQUENCING ASK THAT WAS SUBSEQUENTLY COMMERCIALIZED AND SOMEWHERE BETWEEN WAS THE COMPANY CALLED ASHEN COURT THAT WAS A SPINOFF FROM THE BROAD INSTITUTE AND THOSE ARE BIOSYSTEMS EMERGED FOR LIFE TECHNOLOGIES AND SO FORTH I GUESS I??YES, DIDN’T WE FUND SOME EARLY WORK THAT LED TO THE BIOCHEMISTRY FOR GENOMIC AND THERE’S I. T. THAT WAS CRITICAL WELL SOME OF THE EARLY THINGS THAT I GOT INTELLECTUAL PROPERTY I THOUGHT WERE COPPELLED TOGETHER?? >> NO? >> I’M NOT SURE I DON’T KNOW WHAT THAT WOULD BE >> OKAY >> SO NOW IF YOU’RE TALKING ABOUT THE MUSEUM MAN GENOME PROGRAM, WE DID FIND OF SOME THE SEQUENCING BY HYBRIDIZATION WORK THAT LED TO NAWAS PART OF THE UNDERPINNING YEAH >> AND WE ACTUALLY FUNDED ALUMINA VERY EARLY ON, IT WASN’T FOR THE SEQUENCING TEGGIC??STRATEGICNOLOGY, FOR THE FEE BASED HYBRIDIZATION, AS LONG AS I SHOULD SAY, POLLENATOR SYSTEM, ENJOYED CHURCHES LAB THAT ACTUALLY WAS NOT IN THE PROGRAM MPLET IT WAS FUNDED IN THE GRANT WE FOLDED IT IN BECAUSE IT MADE INTELLECTUAL SENSE AND SPECIFIC BIOSCIENCES WE FUNDED EARLY ON, WHERE IF WAS A SMALL PIN OUT OUT OF CORNELL UNIVERSITY WHERE THE GRADUATE STUDENT WHO IS WORKED ON THE PROGRAM AND THE LAB STARTED A TINY COMPANY TO START DEVELOPING THAT SUBSEQUENTLY WAS FUNDED IN THIS PROGRAM BUT THESE ARE UPDATED VERSIONS OF GENE SHOWN TO SCALE, SOME OF THESE ARE LARGE MACHINES SOME OF THEM ARE BENCH TOP AND SOME ARE DESK TOP MACHINES AND I THINK THAT’S ALL??THE THROUGH PUT OF THESE MACHINE SYSTEM SO GREAT AND ACTUALLY SORT OF THE INFRASTRUCTURE YOU HAVE TO BE ABLE TO SUPPLY THEM WITH SAMPLES AND TO GET DATA OFF AND INTERPRETED, AND MOST OF THESE DEVELOPED SMALLER VERSIONS THAT MIGHT HAVE BETTER APPLICATION IN DIFFERENT SETTINGS, WELL’S A IT THEY WAY BITTEN TUNE TO DIFFERENT SETTINGS SO I DECIDED NOT TO FULL OUT THIS GRAPH, BUT I WANT TO MAKE THE POINT THAT EACH OF THESE SYSTEMS HAS DIFFERENT FEATURES AND THE FEATURES RANGE FROM THE METHOD THAT’S AUSUSED TO GENERATE THE DATA, THE LENGTH OF ARES FROM 50 TO ALMOST A THOUSAND, HOW MANY READS YOU GET PER RUN, HOW MANY GIGA BASES YOU PRODUCE AND SO FORTH, VERY DIFFERENT ARRA MODELS, RUN TIMES AND COSTS SO I THINK THAT’S ACTUALLY A GOOD THING IT’S 1 OF THE FEATURED THAT’S CUBED TO THE??CONTRIBUTE TED??CONTRIBUTED TO THE DEVELOPMENT OF THESE SYSTEMS SO I THINK WE OUGHT TO THINK OF THESE AS KITS WITH A BOLT WITH A NUMBER OF DIFFERENT KINDS OF TOOLS BUT WE HAVE ROOM FOR INNOVATION, LOTS OF NEW IDEAS AND AS I SAY COMPETITION AND THAT’S BEEN IMPORTANT AND I THEN PROGRAM, THE PROGRAM HAS CONTRIBUTED TO THIS THERE ARE LOTS OF DEFINITE APPLICATIONS IN DNA ANALYSIS AND PROTEINS BOUND TO IT THE ANALYSIS AND 1 OF THE KEY FEATURES THAT’S DIFFERENT REAR FROM THE SEQUENCING IS THAT THESE ARE DIGITAL AND IT ALSO IN CONTRAST TO MOST OF THE CHIP METHODS, THE DNA

ARRAY METHODS THAT HAVE BEEN USED IS THESE ARE DIGITAL BECAUSE YOU CAN COUNT EACH OF THOSE FEATURES ORIGINATE FRIDAY A GENOMIC DNA FRAGMENT BUT TECHNOLOGIES HAVE NOT WAITED TO APPLY THE TECHNOLOGIES UNTIL THEY WERE COMPLETELY READY BUT AS THEY WERE BEING DEVELOPED, THEY WERE BEING APPLIED RIGHT AWAY TO A WIDE VARIETY OF PROGRAMS THAT YOU’RE ALL VERY FAMILIAR WITH, THIS HELPED TO PULL THE TECHNOLOGY OUT, TUNE THE TECHNOLOGIES TO MEET THE NEEDS OF THE USERS WHAT ARE THE THROUGH PUT INCREASES, YOU CAN DO THE CALCULATIONS OF THESE MACHINES AND AT THE END OF THE HUMAN DENOME BROG ECTOMYOSIN IT TOOK ABOUT A 3 MONTHS TO SEQUENCE A HUNDRED HUMAN GENOMES, EARLY ON IN RELATING OUT OF THESE SYSTEMS, YOU COULD CALCULATE IT TOOK ABOUT 3 OR 4 MONTHS WITH 1 MACHINE, COUPLE YEARS LATER LESS THAN 1 MONTH WITH 1 MACHINE AND NOW, ABOUT A WEEK OR ABOUT A WEEK OR SO WITH 1 MACHINE BUT THERE’S ENOUGH REAL ESTATE ON THAT CHIP NOW YOU CAN SEQUENCE 3 GENOMES THE SO THAT’S REALLY QUITE STUNNING PROGRESS AND YOU’VE ALL SEEN THIS A HUNDRED TIMES COULDN’T DO ALL THOSE GENOMES IF THEY COST 50 MILLION DOLLAR AND FORTUNATELY IT DOESN’T??CAN YOU SEE THE GROKS OF THESE MACHINES CO INSIDES WITH THE TIMING OF THIS DRAMATIC REDUCTION, THE FIRST NEXT FEW SLIDES ARE OF ENTERS THAT ARE ON THE MARKET AND RECENTLY BROUGHT INTO LABORATORIES 1 OF THESE IS USES STILL SEQUENCING BY SYNTHESIS BUT INSTEAD OF USING LIGHT DETECTION, IT USES ELECTRONIC DETECTION IT USES Ph WHICH IS??PROTONS THAT ARE EVOLVED AS THE POLYMERIZATION REACTION OCCURS AND THIS IS ANOTHER CASE OF SCALING AND AND GRANT THAT ION TORRENT HAS FROM NHGRI IS 1 AGAIN, THEY HAD A COMMERCIALIZATION PLAN, THESE WERE COMING ON THE MARKET AND THEIR GRABT FROM US IS TO SCALE THIS IS AN ANNOUNCEMENT, ERIC REFERRED TO AS THE INTRODUCTION AND HIS DIRECTORS REPORT IS THIS COMPANIES RECENTLY ANNOUNCE THAD LATER THIS YEAR THEY’LL HAVE SYSTEMS THAT CAN SEQUENCE THE GENOME IN A DAY FOR A THOUSAND DOLLARS SEE WE’LL SEE IF THAT HAPPENS BUT THAT WAS WHAT THEIR GRANT WAS CONTRIBUTED TO NORMALLY THEY’RE CLEAR, INESTMENTS, WE’RE INVESTING 20 MILLION DOLLARS A YEAR IN THIS PROGRAM, THE iPAD WEP THESE MACHINES AND HUNDRED 22 MILLION DOLLARS AND WE’RE MAKING SMALL SIGNIFICANT CONTRIBUTION TO THAT AND TO THE DEVELOPMENT OF THE FIELD ANOTHER APPROACH WOULD WATCH DNA POLYMERASE POLARIZED KIEWLS IN ACTION, IN REALTIME IN INSTEAD OF HAVING CYCLES OF CHEMISTRY AND DETECT IN CHEMISTRY, WATCH THE MOLECULE IN REALTIME, THERE ARE A FEW DIFFERENT COMPANIES THAT ARE DEVELOPING THIS TECHNOLOGY VISA GEN AND RECOLLECTS HAVE HAD GRANTS IN NHGRI TO DO THIS AND THE IDEA IS IF YOU SET UP YOUR LIGHT CORRECTLY AND THE DIFFERENT COMPANIES USE DIFFERENT WAYS TO SET UP THE LIGHT, YOU CAN SEE THE FLUORESCENTLY LABELED NUCLEOTIDES OF THE POLYMERASE SO THE BOTTOM FIGURES JUST TO DEMONSTRATE YOU CAN DO THIS, IN A PAPER IN SCIENCE YOU CAN MAKE IN HIGHLY PARALLEL AND THERE’S AT LEAST THE OPPORTUNITY, THE POSSIBILITY OF SOME OF THE READS BEING QUITE LONG WHICH WOULD BE VERY INTRIGUING IF YOU WANT TO BE ABLE TO PUT GENOMES TOGETHER NOT OLDSMOBILE CAN YOU READ GENOME SEQUENCE, BUT CAN YOU READ EPIY GENETIC DATA DIRECTLY OFF OF THE MACHINE YOU DON’T HAVE TO DO THE CONVERSIONS THAT WE DO NOW, THE BIOCHEMICAL CONVERSION AND THIS JUST SHOWS THE POLYMERASE THAT DNA POLYMERASE PAUSE WHEN IS IT SEES A METHALATED BASE FURTHER MORE, CAN YOU READ RNA DIRECTLY OR SHY SAY THEY’RE WORKING ON READING RNA DIRECTLY, AND THIS IS A DEMONSTRATION, YOU JUST SWITCH THE POLYMERASE IN THE SYSTEM ??I HAVE WAY TOO MANY SLIDES FOR THIS BUT THE IDEA IS THAT IF YOU HAD A READER THAT’S THE SAME SIZE OF THE D NA MOLECULE MUCH LIKE A POLYMERASE BUT COULD PERHAPS READ AN ENZYMATIC??IN THIS CASE WE READ THROUGH THE INTERRUPTION OF IONS ON THE FLOOR, THE ION FLOW IS INTERRUPTED DIFFERENTIALLY, AND THE NUCLEOTIDE IS IN THE CHANNEL I SAY??WHY WOULD WE WANT TO DO

THIS, YOU SHOULD BE ABLE TO SEQUENCE GENOMIC DNA, YOUR WORK FLOW WOULD BE SIMPLIFIED IF IT WORKS AT ALL, YOU OUGHT TO BE ABLE TO GET LONG READS THAT’S ALSO LONG READS, YOU COULD DO IT WITHOUT DESTROYING THE DNA IF FOR SOME REASON YOU WANT TO DO THAT, AGAIN, ACGAND T, MODIFIED BASIS, YOU COULD READ RNA 2 ??IN CASE YOU DON’T RECOGNIZE THIS ACCIDENT IT’S A TRI COVEREDDER: SO A NUMBER OF GROUPS ARE WORKING ON THIS WHEN THEY STARTED OFF IN A LIPID BI?LAYER SO THEY STARTED TRYING TO MAKE DEVICES OUT OF HARD MATERIAL USING THE TECHNOLOGIES OF THE ELECTRONICS INDUSTRY AND IT’S AN INCREASING IDEA IT’S BEEN EXTREMELY CHALLENGING PEOPLE DIDN’T KNOW HOW TO MAKE HOLES IN THE RIGHT MATERIAL WHEN THEY WERE THE RIGHT SIDE THIS, STARTED INMENTS BY DARPA AND OTHER AGENCIES TO DO THIS FABRICATION AND HAD IS ACTUALLY NOT GOING INTO THIS, THIS IS DIFFERENT ELECTRONIC DETECTION METHOD THEN WE OUGHT TO BE ABLE TO DISTINGUISH THE SIGNALS OF ACGNT AND SO FAR HAS HAS BT BEEN DONE IN THOSE KINDS OF OF DEVICES AND AGAIN IT’S BECAUSE IT’S HARD TO FABRICATE’S DEVICE WITH THE POSITION AND POSSESSION IT CORRECTLY WITH AVAILABILITY MORE RECENTLY THE STATE OF THIS AS FAR AS I KNOW, PEOPLE HAVE SHOWN THEY CAN MAKE DEVICES, PUT DNA THROUGH IT, AND WHEN THE DNA OLYMPIC KIEWL PASSES THROUGH, NOBODY’S YET BE ABLE TO DETECT THE SEQUENCE THE MOLECULES BUT THE POSITIONING PROBLEM HAS BEEN AT LEAST PARTIALLY SOLVED BY THIS APPROACH WHICH WOULD SURFACE IS THE THE METAL SURFACES SO THAT YOU GET CHEMICAL FINGERS STICKING OUT FROM THE CHEMICAL SURFACES THAT COULD BOND WITH THE TRANSIGENTLY TRANSIENTLY WITH THE DNA MOLECULES AND YOU CAN MAKE THESE AND DISTINGUISH WHEN HAVE YOU A SOLUTION OF NUCLEOICIDES YOU COULD DISTINGUISH BETWEEN THE 4 BASES AND YOU CAN TAKE THAT TO THE NEXT STEP OF DISTINGUISHING THAT THERE ARE DIFFERENT INDIVIDUAL NUCLEOTIDES WITHIN AN OLIGMER, YOU GET DIFFERENT SIGNALS AS YOU YOU GET THERMAL FLUCTUATION AND YOU CAN NOT ONLY DISTINGUISH AMONG THE BASES, BUT YOU CAN DISTINGUISH DIFFERENT METHALATED BASIS WITH THESE DEVICES NOW THIS IS NOT SET UP FOR SEQUENCING, IT’S AN EXPERIMENTAL SYSTEM BUT IF YOU PUT THAT CHEMISTRY INTO AN NANO PORT, MAYBE THAT WOULD WORK THE BEST DEVICE WE HAVE SO FAR WHERE YOU, CHIEF ATOMIC SOLUTIONS IS WHERE YOU DO PROTEINS TO CHANGE THE PROTEIN STRUCTURE SO THIS IS WORKING REASONABLY WELL, NUMBER OF GROUPS AGAIN, THERE ARE GROUPS THAT ARE SITED THIS IS AGAIN AN EXPERIMENT WITH NUCLEOICIDES SOLUTION AND THEN YOU CAN MOVE THIS AND THIS IS A SERIES OF SLIDES I’M NOT GOING TO EXPLAIN POINT I WANT TO MAKE IS NUCLEOICIDES AND THIS IS NOW??DETECTING SPECIFIC NUCLEOTIDE IDENTITY WITHIN AOLILGO BUT IT’S STATIONARY WITHIN THE PORT SO AND IT IS O IT’S NOT MOVING YET AND THIS IS SHOW YOU CAN DO THIS SO HERE’S SORT OF A RANDOM OLIGO WITH EITHER CTGORA, A PARTICULAR POSITION AND YOU CAN DISTINGUISH THAT AND ONCE AGAIN, YOU CAN DO THIS FOR METHALATED BASIS BUT THE BIG PROBLEM WITH WHAT WE’RE TALKING ABOUT SO IS THIS IS LONG CHANNELS SO THERE ARE MULTIPLE BASES IN THE CHANNEL NOW THEY MODIFIED IF BUT IF

YOU COULD CHANGE THE SHAPE OF THE PORE SO THAT IF YOU ONLY HAVE A CHAN KNEEL 1 PLACE, THAT WOULD WORK BETTER AND PEOPLE ARE TAKING THAT APPROACH, TOO AND GETTING VERY STRONG AND VERY WELL DEFINED??WELL DISTINGUISHED SIGNATURES AND THAT’S WITH DNA HANG NOTHING A PORE NOW WHAT ABOUT MOVING THE DNA THROUGH THE PORI WON’T EXPLAIN IT BUT THIS EXPERIMENT DOES, IT MOVES IT THROUGH THE PORE, 1 BASE A A TIME AND CAN YOU DETECT THAT AND HERE’S NOW SORT OF AN EASIER WAY OF MOVING THE DNA THROUGH THE PORE, 1 BASE ATA I TIME THAT’S WHEN A MOLECULAR RATCHET THESE ARE EXPERIMENTS SHOWING THAT AS YOU CHANGE THE VOLTAGE, CAN YOU CHANGE THE RATE AT WHICH DNA MOVES THROUGH THE CORE OKAY IF YOU DIDN’T WANT TO HAVE THAT HAVE A RATCHET BUT JUST WANTED TO SLOW DOWN THE DNA MOVING THROUGH THE PORE, SO THAT YOU WOULD HAVE TIME TO READ THE ELECTRONIC SIGNAL AND EVAPORATE GONE INTO THIS, WHEN YOU ELET THROUGH THESE PORS IT WANTS TO MOVE THROUGH REALLY FAST NOW IF YOU WANT TO HAVE A STRONGER AND PUT IN MORE COLTY I HAVE MORE IONS THE PROBLEM IS WHEN HAVE YOU MORE IONS THAN THE DNA MOVES FASTER SO YOU NEED TO HAVE SOME OTHER WAY AND PEOPLE HAVE SHOWN YOU CAN DO THAT BY MODIFYING THE CHARGE IN THE CHANNEL OR BY BUILDING A TRANSISTOR LIKE DEVICE THAT WOULD VERY FAST ELECTRONIC SWITCHING, YOU WOULD BE ABLE TO RATCHET A DNA MOLECULE THROUGH A BOOR A BASE AT A TIME SO ALL THE PIECES ARE KIND OF THERE AND NOW, WE’RE??PEOPLE ARE WORKING ON TRYING TO PUT THESE TOGETHER AND AND THESE 1S I’VE SHOWN YOU ARE LICENSED TO 2 COMPANIES AND 1 OF THOSE COMPANIES HAS ANNOUNCED, JUST HAD A PRESS RELEASE, A WEEK OR WEEK AND HALF AGO SAYING THEY’RE COMMERCIALIZING THEIR TECHNOLOGY LATER THIS YEAR AND THEY HAVE A BIG TOP COMING UP NEXT WEEK SO WE’LL SEE WHAT THEY SAY SO THIS MAY OR MAY NOT BE SO FAR OFF AND SLOW THE DNA DOWN TO READ A SIGNAL AND SLOW IT DOWN TO 1 MILLI SECOND PER BASE JUST A THOUSAND AND AND IN A DAY THIS IS MICROSCOPY AND THEY HAVE PRELIMINARY EVIDENCE THAT THEY CAN PUT INDIVIDUAL BASES ON THE SURFACE PEOPLE ARE MINIMIZING NOW THE CHALLENGE OF DNA SEQUENCING, WE CAN ALL DO THAT THE PROBLEM IS THE ANALYSIS, MAKING THE LIBRARY, GETTING SAMPLES, THOSE ARE ALL TRUE I WOULD SAY THIS IS A GOOD THING ERIC TALKED MULTIPLE TIMES ABOUT MOVING THE BOTTLE NECKS IT’S GREAT TO BE SUCCESSFUL IN MOVING BOTTLE NECKS NOT ALL THE WAY THERE BUT MOVING ALONG THE PROGRAM, I’M JUST ABOUT WRAPPING UP HERE, THE PROGRAM HAS I MENTIONED LAUNCHED BY??LARCHING OUR RFAs IN THE INFORMATION, A KEY??AND ESEBTIAL COMPONENT OF THIS PROGRAM HAS BEEN THE ANNUAL MEETING WHERE PEOPLE MEET AND SHARE A LOT OF RESULTS, WE WUSH THEM TO SHARE RESULTS AND WE UNDERSTAND EVERYBODY HAS TO HAVE CERTAIN SECRETS, USUALLY THEY HAVE A SECRET FOR A YEAR AND THE NEXT YEAR THEY CAN TALK ABOUT IT OPENLY WE DO TRY TO GET TEEM TO SO WE SORT OF TAKE A LOOK AT STATUS OF THE FIELD AND WHAT ARE THE CHALLENGES WITH THESE MEETINGS ARE ATTENDED BY PEOPLE FROM OTHER AGENCIES OF THE GOVERNMENT SO WE CAN SHARE OUR KNOWLEDGE WITH THEM, THEY SHARE THEIR KNOWLEDGE WITH US THEY FUND OUR GRANTEES THAT MEET THEIR NEEDS AND SO FORTH WE PUBLISHED A BIBLIOGRAPHY AND WHY DOES THIS WORK? THE GRANTEES ARE SHARING INFORMATION A LOT OF INFORMATION THEY CAN TELL EACH OTHER AND LEARN A HUGE AMOUNT AT THESE MEETINGS THEY ARE MOTIVATED WHEN THEY FIND OUT HOW FAST THE FIELD IS MOVING IT GETS EVERYBODY REALLY JAZZED THEY COME PETE AND COME IN, AND PEOPLE ARE NOW??WHO WERE COMPETING ARE NOW

COLLABORATING, THIS IS A GREAT EXPERIENCE FOR THE STUDENTS WHO CAN MOVE FROM 12 ANOTHER AND AS ERIC MENTIONED AGAIN, AN OPEN MEETING ON THE DAY OF THE GRAND MEET SEC EMPLOYEE OR GUARD THEY CAN SPREAD THE JOY, THIS INSTITUTE HAS BEEN COMMITTED THAT IS ABSOLUTELY CRITICAL OF KAREN WAS TALKING ABOUT THINGS THAT HAPPEN BEST AT NHGRI, IRB THINK THIS IS AN EXAMPLE OF THAT THE QUALITY AND THE QUALITIES OF THE PEER REVIEW THIS GROUP, ADVISORS HAVE BEEN WILLING TO TAKE RISKS, I THINK THEY PAID OFF ABOUT TOY WE TO SOME EXTENT FELL AT A GREAT TIME IN THE DEVELOPMENT OF THE FIELD SO WE HAVE DISCOVERY AND THERE’S DEVELOPMENT AND AN INVESTMENT CHAIN CARRY THIS ALL FORWARD SO I WOULD SAY THAT THE TECHNOLOGIES WE’VE DEVELOPED IN THIS PROGRAM THAT WE CAN CONTRIBUTE??DEVELOPMENT WE’VE CONTRIBUTED TO, HAVE REALLY CHANGED THE FACE OF GENOMIC SCIENCE AND IT’S STRAY TRAJECTORY AND I HAD TAKEN THIS OUT AND BUT AFTER KAREN’S A DECIDE I WOULD PUT IT BACK IN BECAUSE I THINK THEY SPAN THE PURVIEW OF WHAT TECHNOLOGIES ARE TRYING TO DO SO THANKS AND I’LL TRY TO ANSWER QUESTIONS >> OKAY, NEEDLESS TO SAY THIS IS THE EASYST JOB IN THE WORLD WHEN HAVE YOU PROGRAMS LIKE THIS JUST REMARKABLE >> YOU SAID FRACTIONS BUT WHAT PERCENTAGE GO TO DOLLARS OR COMPANIES AND I VICTORY DIVIDE TODAY UP BY COMPANY DOLLARS??I HAVEN’T DIVIDED AND GROUP VS BEEN SUPPORTED BUT AGAIN, SOME OF THOSE GROUPS HAVE MORE THAN 1 GRANT SO IT’S NOT 45 GRANTS, BUT 45 ACADEMIC GROUPS AND 19 COMPANY GROUPS ??AND THE SIZES OF THE GRANTS ARE SBIR, SO THEY’RE PHASE 1, AND 20 IN THE COMBINATION SETTINGS AND SOME OF THEM ARE NOT SO IT’S INTERESTING AND I KNOW YOU??I’VE REVIEWED FOR YOU BEFORE AND I KNOW WHAT SOME OF THE ISSUES ARE HERE, YOU HAVE TO HAVE, IT IS REALLY GOOD THAT THE COMPANIES ARE BEING SUPPORTED ARE BEING INTERESTED BECAUSE THIS IS NOT GOING TO GET COMPLETELY DONE IN ACADEMIA, ALTHOUGH A LOT OF IDEAS KIND OF START THERE, I THINK YOU SAID SOMETHING ABOUT A YEAR OF SECRET EVENTS OR SOMETHING? >> YEAH, SO SOME PEOPLE COME TO THIS MEETING AND THEY ARE JUST??THEY’RE JUST HAPPY THEY’RE VERY ACADEMIC PERSPECT AND I HAVE LOVE TALKING ABOUT THESIS RESULTS I’VE HAD A FEW GRANTEES, ACADEMIC GRANTEES WHO ARE JUST SO WORRIED THAT, YOU KNOW, THEY WANT TO COMPLY WITH THE PROGRAM, THEY WANT TO BE ABLE TO TALK ABOUT A LOT OF THEIR STUFF, BUT THERE ARE A FEW THINGS THEY’RE NOT QUID READY TO DIVULGE ALL THE DETAILS AND I TRY TO PUSH THAT TO DIVULGE AS MUCH AS THEY CAN BUT I UNDERSTAND ON THE OTHER HAND IF THEY DON’T GET PATENTED AND LICENSED THEY WON’T GET DEVELOPED SO I TRY TO REACH THE HELPY MEDIUM >> THAT’S WHY I RAISE THE POINT, I THINK YOU’RE DOING A GREAT JOB OF BALANCING THAT YOU HAVE TO PROTECT IT THESE WON’T EVER GET DONE, YET OUR INCLINATION IN THE GENOME INSTITUTE IS FOR EVERYTHING TO BE FREELILY AVAILABLE >> WE CAN’T DO THAT >> I THINK YOU’RE DOING IT JUST RIGHT BECAUSE YOU DO NEED BOTH AND YET, AT LEAST THE 1 REVIEW WHERE I DID A FEW YEARS AGO, I WAS??IT WAS REMARKABLE TO ME HOW MANY OF THEM ARE IN EACH OTHER’S FACES SOME OF THEM ARE IN MULTIPLE KIND OF COMPETING BY THE GRANDEES OR THE SCIENTIST ARE >> YEAH, EVEN WHEN PEOPLE ARE KEEPING SOMETHING TO THEMSELVES, THEY HAVE SO MUCH KNOWLEDGE AND THEY CAN SHARE THAT AND IT REALLY ACSEMESTERERATES THE FIELD >> ??ACCELERATES THE FIELD >> [INDISCERNIBLE] >> COULD YOU IDENTIFY YOURSELF, PLEASE? >> [INDISCERNIBLE] >> OKAY, YEAH, SO THE QUESTION, IF I HAVE THE QUESTION RIGHT, MAYBE STAY AFTER A SECOND TO SEE IF

I??BECAUSE I’M NOT QUITE SURE WHICH NUMBER, SO, THE COSTS HAVE COME DOWN FROM SOMETHING TO 50 MILLION DOLLARS TO SOMETHING AND WHAT QUALITY DO YOU GET FOR THAT AMOUNT OF MONEY AND SO, I WOULD SAY THAT WE’RE PROBABLY CLOSE NOW TO THE HIGH QUALITY DRAFT WITH A LOT OF THE SEQUENCING THAT’S BEING DONE, YOU KNOW 30 FOLD COVERAGE ON THESE SHORT READS, YOU CAN USE THAT TO MAP, 2 KNOWN GENOMES AND PEOPLE ARE GETTING BETTER AND BETTER AS A DEVELOP ALGORITHMS TO DO ASSEMBLY THERE ARE A BUNCH OF TRICKS CAN YOU DO IN MAKING LIBRARIES TO DO THE ASSEMBLYS BUT YOU CAN GET A REASONABLY GOOD PUT TOGETHER GENOME FROM THIS COMBINATION OF JUST MAPPING TO A REFERENCE AND SOME ASSEMBLY SO??THAT COST IS NOW IN ROUGHLY IN THE 5000 TO $10,000 PER GENOME RANGE THAT’S GOOD ENOUGH TO DO A LOT OF CLINICALLY RELEVANT RESEARCH AND SOME CLINICALLY??ACTUALLY SOME CLINICAL APPLICATIONS YOU’VE SEEN THE PAPERS WHERE PEOPLE ARE FINDING, YOU KNOW DISEASE GENES AND GIVING HINTS IN CASE SM CASES GIVING HINTS TO A THERAPY BUT I THINK THAT IS THE LAST COUPLE ROUNDS OF RNA, WE’RE SAYING, YOU KNOW, IF WE SET A HELPED DOLLARS GENOME OR A $50 GENOME BACK IN 2004, PEOPLE VALID THOUGHT WE WERE NUTS, NOW PEOPLE SAY, WELL, WHY ARE YOU TALKING ABOUT A THOUSAND DOLLAR GENOME WELL, WHOA, YOU KNOW, BUT WE ARE TALKING ABOUT, A THOUSAND DOLLARS OR LESS AND WE REALLY DO NEED TO TALK ABOUT IMPROVED QUALITY WE FRAMED THIS IN TERMS OF COST AND I THINK THAT’S PROBABLY THE RIGHT THING TO DO BUT WE HAVE A LONG WAY TO GO, I THINK IN TERMS OF THE QUALITY OF SEQUENCE THAT WE WOULD LIKE TO ACHIEVE >> OKAY, FIRST OF ALL, I THINK JEFF DID A TREMENDOUS JOB IN THIS PROGRAM WATCHING IT PROGRESS AND SEE ALL THE RESULTS AT SUCH SPEED HAS BEEN EXCITING THIS COMMENT ON YOU SAY IT’S BEEN ABOUT 20 MILLION A YEAR YOU PUT INTO THIS AND IT MIGHT BE INTERESTING TO MAKE A FEW COMMENTS ABOUT HOW THE TECHNOLOGIES TRY TO GET FAST TRACK IN TERMS OF ADOPTION BECAUSE MY HAPPENING IS THAT A LOT OF THESE TECHNOLOGIES ARE PUT INTO THE LARGE SCALE SEQUENCING CENTERS AND OTHER THINGS WHO WHERE THE EVENTS MAY BE FASTENER TERMS OF ADOPTION AND I DON’T KNOW HOW THAT FACTORS IN TERMS OF THE COSTS OR NHB RI >> YEAH, SO, THE??I GUESS THE CLOSEST I COULD COME TO THAT IS TO SAY THAT THE CENTERS BUDGETS AND RICK COULD COMMENT ON THIS, FOR AT LEAST IN THE MOST RECENT SEVERAL YEARS, WE’VE FIGURED THAT THE CENTERS ARE INVESTING SOMEWHERE ON THE ORDER OF 10% OF THEIR??OF THEIR OVERALL BUDGETET ON IMPLEMENTING NEW TECHNOLOGIES AND THAT’S BEEN A REALLY IMPORTANT COMMENNENT OF THE ADVANCES IN THESE TECHNOLOGYNOLOGYS, SO WHAT I’M TALKING ABOUT HERE IS REALLY EARLY STUFF, REALLY RESEARCHING STUFF, SO THEN IS PASS THES OUT OF THE PURVIEW OF WHAT THIS PROGRAM AND DO IS COMMERCIALIZATION AND DEVELOPMENT AND THAT’S WHERE THE EXPERIENCE OF OF SOPHISTICATED USER SYSTEM UNBELIEVABLY IMPORTANT BECAUSE ALL THESE COMPANIES ARE PUSHING TO GET THEIR SYSTEMS OUT AND AND THEY USUALLY DO IT TOO EARLY THE INFORMATION THEY GET BACK FROM SOPHISTICATED USERS, MAKES A HUGE CONTRIBUTION TO THE SUCK SUCCESSFUL COMMERCIALIZATION >> JUST REAL QUICK, JEFF, YOU MAY HAVE SAID AND I DON’T??I HAVEN’T NOTICED TARGETTINGLY SEQUENCING, FOR $10, BUT IN FACT, FOR CLINE CAM APPLICATIONS AND BEING ABLE TO SEE A HUNDRED GENES AND DEEP SEQUENCING IT FOR REALLY CHEAP AND REALLY VALUABLE >> WHAT WE DID WITH THIS PROGRAM, WAS WE SAID, THIS IS TO INVENT NEW SEQUENCING TECHNOLOGIES REALLY COMPLETELY SOMETHING DIFFERENT WE DO NOT SUPPORT PROJECTS THAT ARE SPECIFICALLY TO IMPLEMENT A NEW WAY TO GATHER UP THE TEMPLATES WHAT WE SAID IS IF YOU HAVE AN IDEA OF HOW TO DO THAT AND CAN YOU SPIN THAT ALONG IN THE COURSE OF DEVELOPING A NEW TECHNOLOGY THAT CAN YOU USE FOR A WHOLE GENOMES, THEN WE WOULD CONTRIBUTE TO THAT, BUT THE FACT IS, THAT APPLICATIONS AND CAPTURE EXOHMS DO REALLY WELL IN THE STANDARD STUDY SECTION SAYSS NHGRI SUPPORTS A LOT OF THAT WORK THAT’S NOT INCLUDED HERE I MEAN THEY DON’T NEED TO BE UJ HUGE >> THEY DON’T NEED TO GO THROUGH THE SPECIALIZED REVIEW >> I WAS ESPECIALLY INTERESTED IN THE TABLE YOU DIDN’T FILL IN AND?? >> I DELETED IT ALL BECAUSE IT’S HARD TO KEEP UP WITH AND THAT THEN WHO DO YOU BELIEVE!

>> RIGHT WHAT I WAS GOING TO IMAGINE IS FROM AN NHGRI PERSPECTIVE IT SEEMS IMPORTANT THAT THAT BODY COULD GIVE REALLY IMPORTANT GUIDANCE INTO WHICH OF THOSE COLUMN SYSTEM INCREASINGLY IMPORTANT IN OTHER WORDS COST FOR EXAMPLE IS DECREASING IN IMPORTANCE AS ALL THIS COMES DOWN BUT THINGS LIKE ACCURACY READ LENGTH MAY BE VERY MUCH INCREASING IMPORTANCE SO PRIORITIZING WHAT’S IMPORTANT FOR THE NEXT WAVE WILL BE REALLY IMPORTANT LIKE THAT SO THAT’S REALLY HOW TO FRAME THAT AND MEN AND WOMEN ROLE NHGRI CAN PLAY EFFECTIVE AND SOME OF THAT IS DONE WELL IN INDUSTRY >> CHANNEL >> RIGHT >> ANY LAST QUESTIONS? FOR JEFF? IF NOT WE ARE FUNDAMENTALLY ON TIME AND WE HAVE TO MAKE A COMMAND DECISION HERE