Commercialization of HaploSeq as a Service (HaaS) for generating chromosome-span phased genome and exome sequence information

Commercialization of HaploSeq as a ServiceHaaSfor generating chromosome span phased genome and exome sequence information Arima Genomics SPECIFIC AIMSProject Summary Abstract Overof Next Generation SequencingNGSis sequenced via Illumina short read sequencersThis is because of its cost effectiveness and faster turn around timesHowevershort read sequencing technologies lose critical contiguity information and are limited in assembling genomes de novo and reconstructing maternal and paternal haplotypes of diploid genomesContiguity information is valuable for understanding the genetics of human health and diseaseand therefore critical for advancing precision and personalized medicineLongread technologiese gPacific Biosciencesonly reach megabase scale chromosomal contiguitybut isX more expensive than Illumina short readlimiting its useRecent advances in DNA preparation can preserve long range information that is compatible with Illumina short read sequencingThesesyntheticlong readsor SLRmethods can improve short read technologies withlong range contiguity and short read economyHoweverthe maximal SLR contiguity is onlythe contiguity aMb average human chromosomeTo construct multi megabase contiguitySLR methods require genomic DNAgDNAfragments andgtKbbut obtaining long gDNA fragments is challenging and this limits current SLR methodsArima Genomics has optimized HiC technologyan SLR based DNA protocolto establish Arima HiCA HiCthat preserves chromosome span contiguity for de novo assemblyhaplotype phasing and metagenomicsthe libraries of which can be sequenced via Illumina short read instrumentsA HiCrather than using purified gDNAleverages the long contiguity information preserved naturally in thedimensionalDorganization of genomes in cellsIndeedD information is not only long range but in fact full chromosome range informationA HiC optimizes multiple features of HiCwhile HiC is laborioustime consumingday procedurecostly protocolA HiC is easy to performgenerates consistent quality librariesandgtless cost and is only ahour protocoland is compatible to standard library preps such as KAPA Hyper prepstogetherthese properties of A HiC make them automatableAfter success with manual automation viawell plateswe propose to use liquid handlerin partnership with Agilentto automate A HiCand furthermorewe aim to make A HiC robust to wide range of sample typescellstissuesbloodhuman and non humanto serve diverse customers via the automated service platformreferred to as HaaSIn addition to optimizing experimental A HICwe develop several algorithms to generate chromosome span phase information of genomes and exomeswhich we will publish as open source softwareOSSWe also leverage existing OSS for other HiC based appsand together we will automate software for all HiC enabled apps in supercomputing infrastructure to enable quick turn around time for our diverse customersTogetherHaaS architecture has automated experimentalA HiCand computational aspectsOSS for HiC based appsMany commercial playerse gNovogeneprovide sequencing servicesArimaandapos s HaaS provides chromosomal contiguity and thus is differentiated from the traditionalcategoryservice providers such as Novogene who provide fragmented contiguity based on short read or long read methodsIndeedwe propose to collaborate with NovogeneWe are also in communication with PacBio for a potential collaboration and marketing agreementOn the other handwe compete directly with categoryplayers who offer HiC servicesspecifically for de novo assembly applicationNonetheless HiC services from other categorycompanies suffer significant limitationshigh pricesandgt $while Arima prices at andlt $for large genomes and andlt $for small genomeslow quality data via usage of traditional HiCwhile Arima uses optimized A HiCnonautomatable traditional HiCwhile Arima uses fully automatable A HiCand in additionwe have developed specialized phasing algorithms to garner wide customer baseTo dateArima has barely marketed our servicesbut word of mouth has garnered new customers for Arima and attracted repeat businesswhich reflects the quality of Arimaandapos s services and demonstrates significant market demand for Arimasetting the stage for rapid growth to be supported by more deliberate traditional marketing of our proposed HaaS business modelIn this proposalwe develop and benchmark HaaS via collaboration with Key Opinion leaders across multiple sample typesbloodcellstissueshuman and non human samplesfor several HiC based apps Commercialization of HaploSeq as a ServiceHaaSfor generating chromosome span phased genome and exome sequence information Arima Genomics Project Narrative Next generation short read sequencinge gIlluminahas advantages of pricespeedaccuracyand broad adoptionWith short read sequencinghowevera key principle in genomics is severely limitedcontiguitya measure of fully linked DNA sequenceContiguity in the context of haplotype phasing to delineate maternal and paternal copies and de novo assembly is critical to understand the structure and function of the genome and for genomics based medicineSeveral companies have attempted to improve contiguity with long read or synthetic long read technologies by increasing read lengthor bar codingor reconstituting artificial chromatinThese methods are limited toof the actual contiguity of an average human chromosomerequire specialized and expensive equipmentand are technically demandingArima has overcome these deficiencies by using HiC methodologya method that can generate chromosomal contiguityWe have optimized HiC protocol to result inwell compatiblehighlyreproduciblehourand low cost protocol referred to as Arima HiCA HiCVia this proposalArima aims to automate A HiC and the associated computational applicationsappsfor phasing and other applications such as de novo assembly and metagenomics through the HaaS architectureHaaS service will receive sampleswhich are put through A HiC DNA prep protocol and standard library prep in an automated fashionimplemented on a liquid handlerand will be subjected to standard Illumina short read sequencingThe data from this experiment can be analyzed to reveal chromosome span contiguity for de novo assembly or phasing of genomes and exomesHaaS aims to serve diverse customers with maximum contiguity and genomic informationat low cost and fast turn around time