Welcome to the new SBIR.gov, to assist in getting you situated with the system, a preview of the new login and registration process is available here. Please reach out to the website support team with any questions via sba.sbir.support@reisystems.com
Company
Portfolio Data
Back to Company SearchARIMA GENOMICS, INC.
UEI: PKRJJSZRJ6M3
Number of Employees: 35
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
SBIR/STTR Involvement
Year of first award: 2015
3
Phase I Awards
7
Phase II Awards
233.33%
Conversion Rate
$1,294,378
Phase I Dollars
$15,760,763
Phase II Dollars
$17,055,141
Total Awarded
Awards
Scalable single-cell workflow for multiomic analyses of chromatin interactions, accessibility, gene expression and cell surface proteins to unravel mechanisms of cellular diversity
Amount: $2,097,684 Topic: 400
Scalable single-cell workflow for multiomic analyses of chromatin interactions, accessibility, gene expression and cell surface proteins to unravel mechanisms of cellular diversity Arima Genomics Project Summary/Abstract All cells in the human body carry the same DNA sequence and yet individual cells are highly diverse in identity, morphology, proliferation, and function, leading to enormous heterogeneity in the context of tissues, organs, and organisms. Individual cells achieve this diversity via unique gene regulatory programs – where in, unique sets of regulatory elements (REs) precisely instruct each cell which genes to express and when. Mapping such gene regulatory programs are central to molecular biology and genomics, as mis-regulation is a major cause of disease – mapping not only helps in diagnosis but also enables therapies that can intervene and correct mis-regulation. Single cell ATAC sequencing (scATAC) has emerged as the popular mapping assay to delineate REs unique to each cell. When scATAC is performed alongside single cell RNA sequencing (scRNA), the researcher has access to both REs and gene expression, allowing them to obtain unprecedented insight into the gene regulatory programs of living cells. There is only one problem – there are often multiple REs in the neighborhood of a gene and without the ability to link specific REs to its target genes, a mechanistic view of gene regulation is lacking, limiting our ability to enable precise diagnosis and drug discovery programs. High throughput chromatin interaction capture assay and sequencing (HiC) presents a three-dimensional view of the genome, often informing the missing link between RE and their target genes. Indeed, several KOLs – e.g., Dr. Tomi Pastinen calls scATAC, scRNA and scHiC as the “trifecta of modalities” that can truly delineate gene regulatory programs of individual cells (see Dr. Pastinen’s letter and 30+ additional letters of support). Recognizing the value, several academic labs have developed scHiC protocols, which has already unraveled incredibly detailed mechanistic insights of gene regulation of complex microenvironments including breast cancer, prostate cancer, hippocampus – several of these studies are discussed in this application. Despite the enthusiasm around scHiC data, adoption has been restricted to a few labs because of (1) severe experimental inefficiencies that result in exorbitant costs (upwards of $20,000 per sample), and (2) because current scHiC protocols involve complex plate- or combinatorial indexing workflows that are challenging to setup and execute. Via a self-funded phase-1 program, we tackled problem (1) to drastically improve efficiency of scHiC and consequently, drive costs down from earlier $10 per cell, to <$2 per cell, details of which are discussed both in research and commercial plans. We then used our rigorous product development expertise to translate the resultant scHiC chemistry into kits that were extensively validated by multiple KOLs (see letters from Joe Ecker, Longzhi Tan and others). Upon validation, these KOLs have become customers using Arima’s scHiC, referred to as A-scHiC kits, in their single cell workflows instead of the inefficient former academic protocols. Webinars and conference presentations from these early adopters created a ripple in the community and in a span of few months, we have sold >1,000 reactions of A-scHiC kits to tens of academic labs (despite no marketing activity from Arima), who have embedded our kits within both the plate- and combinatorial indexing single cell workflows. The scope of phase-2 program is to tackle problem (2) to enable widespread adoption. In particular, we propose to build off the A-scHiC chemistry toward what we refer to as the sc3DGR chemistry that is performed upstream of 10X genomics (10XG) Chromium – i.e., the output of sc3DGR kit will be an input into the 10X ATAC (flavor1) or 10X Multiome (flavor2) kits, to concurrently capture scHiC and scATAC (flavor1), or, scHiC, scATAC and scRNA (flavor2), respectively. Such a chemistry will not only solve the ease to use problem (2) given its combability with the market leader 10XG, but importantly, it will enable multiomic analyses of the “trifecta” from the same individual cell concurrently, thus enabling cell perturbation, characterization and screening use-cases for precision mapping, diagnosis, and therapy. Once the sc3DGR chemistry is finalized, we translate it into robust kits, to be validated by 14 KOLs (see letters of support) across academia and pharma (AbbVie, AstraZeneca & Genentech). For Arima, the chemistry, the informatics, the easy end-to-end workflows, the overall workflow cost, the KOL-based go-to-market strategy – all play major factors in a seamless commercialization process of this leapfrog technology for delineating gene regulation programs of individual cells.
Tagged as:
SBIR
Phase II
2023
HHS
NIH
Developing a kit-based research use only (RUO) translocation assay for deployment as a lab developed test (LDT) toward changing outcomes for patients with driver-negative tumors
Amount: $3,983,315 Topic: NCI
Developing a kit-based research use only (RUO) translocation assay for deployment as a lab developed test (LDT) toward changing outcomes for patients with driver-negative tumors (RFA sub-section: Technology platform for Cancer Diagnostics) SUMMARY Nearly 1M patients are diagnosed with advanced stage cancer per year. One case dear to Arima is a teenage girl who was diagnosed with advanced brain cancer. Her tumor had been tested twice using state-of-the-art NGS-based lab developed tests (LDTs), but no actionable genetic driver could be found, classifying her tumor as “driver-negative”, precluding access to targeted therapies and greatly reducing her likelihood of survival. However, thanks to the parental phase-2 award, Arima had just developed an NGS technology platform – the T-Seq kit – to detect tumor driving translocations and gene fusions from tumor biopsies. Lo and behold, when T-Seq analyzed this patient’s tumor, it revealed a translocation implicating PD-L1, triggering a series of events leading to treatment with pembrolizumab and 9 months later no signs of tumor, all thanks to T-Seq. This proposal strives to scale this clinical origin story to make a widespread impact in the 50% of patients with advanced cancers and no detectable genetic drivers (~488,000 patients per year in US). However, to make this widespread impact, T-Seq technology must be made available to oncologist and pathologist in the form of an LDT. The overarching goal of this proposal is to execute all necessary steps to develop and validate T-Seq kits so that they can be supplied to CLIA labs who will validate and deploy T-Seq as an LDT to inform clinical care. Thanks to our parental phase-2, execution towards this goal has already begun. From a tech perspective T- Seq kits are more sensitive than existing tech because they profile translocations through the lens of a spatial 3D genome, rather than a linear genome, enabling detection of tumor driving translocations like PD-L1 that are otherwise missed. T-Seq technology has also been productized, meeting all the key product products for deployment as an LDT, culminating in the launch of a kitted end-to-end T-Seq workflow. Lastly, T-Seq kit performance is concordant with existing tech, yet it detects tumor-driving translocations in 54% of driver- negative tumors, including 4 patients where the course of clinical care has been altered thanks to T-Seq. With a product in hand and foundational clinical data, the proposed aims accomplish the remaining steps towards our goal of becoming a tech provider to CLIA labs. Specifically, this proposal first aims to establish competitive analytical performance metrics for T-Seq. Then it aims to demonstrate clinical validity and utility of T-Seq across mainline tumor types, and in clinical contexts of severe unmet need. Lastly, the proposal aims to validate and deploy T-Seq kits in partnering academic and commercial CLIA laboratories. The success of each proposed aims is measured using multiple quantitative metrics relevant to that aim, informed by CLIA assay validation guidelines and key metrics defined by stakeholders in the LDT ecosystem. By the conclusion of the phase-2b program, the ultimate goal of becoming a technology provider to CLIA labs will be accomplished, whereby T-Seq kits will be deployed as LDTs in initial academic and commercial CLIA labs, and clinical data, publications, and awareness of T-Seq will be established to accelerate future adoption of T-Seq as an LDT.
Tagged as:
SBIR
Phase II
2023
HHS
NIH
A scalable kit-based assay for multi-omic analyses of transcriptional protein binding and chromatin interactions from ultra-low input frozen and FFPE samples at single-cell resolution
Amount: $2,100,254 Topic: 172
A scalable kit-based assay for multi-omic analyses of transcriptional protein binding and chromatin interactions from ultra-low input frozen and FFPE samples at single-cell resolution Arima Genomics Project Summary/Abstract Precise regulation of gene expression is paramount to establishing cellular identities, and mis-regulation of genes causes human disease. Cells regulate gene expression using regulatory elements (REs), short DNA sequences embedded throughout the genome, who are bound by transcriptional proteins (TBPs) to facilitate their regulatory function. Molecular mapping tools, such as Chromatin immunoprecipitation with sequencing (ChIP-seq), produce “maps” of REs along the genome and have been a ubiquitous approach towards understanding gene regulation. However, REs mapped using ChIP-seq are only understood in context of a linear genome. In reality, REs execute gene control within a three dimensional (3D) genome. Therefore to truly understand gene regulation – gene regulation must be mapped in 3D. Indeed, high throughput chromatin interaction capture (HiC) was developed to produce 3D interaction maps of all 3 billion bases in the human genome, however, HiC does measure transcriptional protein binding, nor whether an interaction is regulatory, thus having limited utility in advancing our understanding of 3D gene regulation. To truly obtain 3D gene regulation maps, a multi-omic assay that concurrently captures the binding of transcriptional proteins and their mediated interactions is necessary. Recently, novel approaches attempt to combine the molecular steps of ChIP-seq and chromatin interaction capture to measure transcriptional protein binding and mediated chromatin interactions in a single, multi-omic assay. However these approaches, termed ChIA-PET and HiChIP, do not efficiently capture chromatin interactions or transcriptional protein binding, respectively. Consequently, there is need for improved assays that produce true multi-omic maps of 3D gene regulation. To satisfy this unmet need, we have developed and commercialized our optimized minimal viable product (MVP) Arima-HiChIP (A-HiChIP) solution. This phase-1 product incorporates innovations designed to meet the needs of early adopter customers, achieving efficient multi-omic mapping of TBP and chromatin interactions in higher input frozen cells and tissues, and a defined subset of transcriptional proteins. We have also developed our phase-1 product for workflow integration, leveraging industry and academic partnerships to reduce barriers in ChIP and bioinformatics components of the workflow, respectively. Our team has deep expertise in the science of chromatin interaction capture, gene regulation, and its commercialization. In 2018, we commercialized Arima- HiC kits for studying general principles of chromatin interactions and within 2 years have accumulated 500+ customers, providing tools to enable published discoveries across a host of basic science and disease research. Based on VOC analytics, we shifted our focus to develop the A-HiChIP kit - a more relatable product to the gene regulation market that customers wanted and that represented a larger market opportunity. Indeed, after our self-funded phase-1 RandD and product developments, we launched our MVP A-HiChIP solution into the market and have seen remarkable success – measured by an increase in our revenue contributions, increased quality of revenue, and traction with key opinion leaders (KOLs), large consortia, and COVID research. However, our phase-1 A-HiChIP has known limitations. In particular, the product falls short of meeting the needs of researchers utilizing common clinical samples types or quantities in their research, or seeking single-cell resolution in their analyses of heterogeneous tissues. As part of this direct-2-phase II program, we propose to further develop our technology to overcome these limitations, meet customer need, and enable broader adoption and application of this powerful multi-omic assay in the form of our second-generation A-HiChIP solution. Specifically, we propose assay developments to enable compatibility with pervasive clinical sample characteristics - ultra-low cell inputs (lt100K cells) and FFPE tissues. Further, we propose development of a first-of-its-kind single-cell HiChIP assay and companion bioinformatics tools. We also propose essential product developments, to ensure commercialization of a robust, premium- performance kit-based product that is optimally integrated into the bulk and single-cell sequencing ecosystems. Upon successful completion of these technical and product-oriented aims, we propose to benchmark and validate our phase-2 A-HiChIP solution through collaboration and prototype (beta) kit and bioinformatics evaluations with KOLs across customer segments.
Tagged as:
SBIR
Phase II
2021
HHS
NIH
A low-input compatible, end-to-end kitted HiChIP workflow for concurrent analyses of transcriptional protein binding and chromatin interactions toward a mechanistic understanding of gene regulation
Amount: $2,056,891 Topic: 400
A low-input compatible, end-to-end kitted HiChIP workflow for concurrent analyses of transcriptional protein binding and chromatin interactions toward a mechanistic understanding of gene regulation Arima Genomics Project Summary/Abstract Precise regulation of gene expression is paramount to establishing cellular identities, and mis-regulation of genes causes human disease. Cells regulate gene expression using regulatory elements (REs), short DNA sequences embedded throughout the genome, who are bound by transcriptional proteins to facilitate their regulatory function. Molecular mapping tools, such as Chromatin immunoprecipitation and next gen sequencing (ChIP- seq), produce “maps” of REs along the genome and have been a ubiquitous approach towards understand gene regulation and define cell types and states based on unique RE signatures. However, these locations of REs are only understood in context of a linear genome. In reality, REs execute their gene control within a three dimensional (3D) genome. Therefore to truly understand gene regulation – gene regulation must be mapped in 3D. Indeed, high throughput chromatin interaction capture (HiC) was developed to produce 3D interaction maps of all 3 billion bases in the human genome. HiC has facilitated discovery of several fundamental principles DNA folding in 3D, including cases where DNA mis-folding contributes to disease. However, HiC does measure transcriptional protein binding, nor whether a chromatin interaction is regulatory, thus having limited utility in advancing our understanding 3D gene regulation. Recently, novel approaches attempt to combine the molecular steps of ChIP-seq and chromatin interaction capture to measure transcriptional protein binding and mediated chromatin interactions in a single assay. However these approaches, termed ChIA-PET and HiChIP, do not efficiently capture chromatin interactions or transcriptional protein binding, respectively. Therefore, there is dire need for improve methods that truly facilitate mapping of gene regulation in 3D. We satisfy this unmet need via our highly optimized, first generation HiChIP solution, Arima-HiChIP (A-HiChIP), that demonstrates efficient and reproducible mapping of transcriptional protein binding and chromatin interactions in cell lines, with higher cellular inputs and a limited set of transcriptional proteins. Our team has unmatchable expertise in the science of chromatin interaction capture and its commercialization. First, we commercialized Arima-HiC kits in 2018 for studying general principles of chromatin interactions and generated $1.2M in revenue in the 1st year of commercialization and $2M in revenue in the 2nd year, with 500+ customers, and 100% growth from 2018 to 2019. Based on VOC analytics, we shifted our focus to develop a more relatable product to the gene regulation market – A-HiChIP - that customers wanted and that represented a larger market opportunity. Indeed, after our self-funded phase-1 RandD and commercial developments, we launched our first generation HiChIP solution into the market and have seen remarkable success – measured by HiChIP growing from 19% to 40% of our revenue contributions, increased quality of revenue, and traction with KOLs, large consortia, and COVID research. However, these kits are limited in terms of the capabilities – they are not robust to a range of transcriptional proteins, they are not optimized towards tissue samples, and they are not optimized towards lower sample input quantities. To enable broader adoption and discovery, we have shown the development towards our second-generation A-HiChIP solution, with advancement towards low sample inputs, tissues, and a broader range of transcriptional proteins. We validate the technology on internal samples provided by academic collaborators and externally in customer hands via prototype beta kits. As part of this direct-2-phase II program, we propose to further develop our technology into truly robust, low input compatible, end-to-end kitted HiChIP solution for concurrent analysis of transcriptional protein binding and chromatin interactions in tissue samples and across a host of important transcriptional proteins. We also propose rigorous and essential product development experiments, to ensure commercialization of a robust, premium- performance kit-based product that is optimally integrated into the ecosystem. Upon successful completion of the technical and commercial developments in Aims 1 and 2, we propose to benchmark and validate the our next- generation HiChIP solution through collaboration and prototype (beta) kit and bioinformatics evaluations with key opinion leaders (KOLs) across customer segments.
Tagged as:
SBIR
Phase II
2021
HHS
NIH
Commercialization of a highly-sensitive, scalable and low-input compatible kit-based solution for discovery of translocations from FFPE tumor biopsies
Amount: $1,998,546 Topic: NCI
Commercialization of a highly-sensitive, scalable and low-input compatible kit-based solution for discovery of translocations from FFPE tumor biopsies Arima Genomics Project Summary/Abstract Despite decades of research, cancer takes the lives of nearly 600,000 people every year in the US. The cancer research community has made key advancements towards improving the precision of cancer diagnosis and recently substantial efforts have been put forth into the genetic profiling of tumors. Specifically, efforts have been focused on developing methods to profile genetic alterations such as translocations that are prognostic in cancer. Knowledge of an individualandapos;s translocation profile can be used to uncover the mechanistic basis of cancer, accelerating cancer research towards development of new precision therapies. Current standard, including NGS, are limited in their ability to characterize translocations. This is because for NGS (WGS or gene panel seq.) to profile translocations, breakpoint-spanning reads are needed and NGS does not enrich for such reads. FISH enriches for breakpoint info by capturing spatial conformation of the genome within cells and but it has limited utility due to its low-throughput nature and its requirement of apriori info of the translocation partners. Spectral Karyotyping (SKY) needs living cells and cannot be performed on FFPE samples, which is a major sample type for cancer samples. Altogether, a method that is (a) high-throughput along the lines of NGS; (b) enriches translocations along the lines of FISH; (c) not requiring apriori indo of translocating partners to enable promiscuous translocation detection; and (d) compatible with FFPE samples – would result in a highly sensitive and scalable solution for translocation discovery. We satisfy the unmet need via a leapfrog solution. We use HiC to capture conformation on the lines of FISH and couple it with NGS (HiC-Seq) to detect translocations at high sensitivity, high precision, high PPV and low FP. Our team has unmatchable expertise in the science of HiC and its commercialization. Specifically, we commercialized Arima-HiC kits in 2018 for studying conformation in the context of Epigenetics research and generated $1.2M in revenue in the 1st year of commercialization with 200+ customers, all from 1 sales executive. However, these kits are not compatible to FFPE, is manual, labor- and time-intensive and cannot handle batches of andgt;10-20 samples at a time – to enable broad adoption toward cancer research, we have shown the development a boxed kit, the “T-Seq Kit”, based on enhanced HiC optimized for performance, speed, ease of use that is compatible to low-input FFPE, fresh and frozen samples. We validate the technology development from sample to insight in a patient-derived FFPE GIST biopsy and demonstrate that we can sensitively profile translocations even from low tumor purity samples (or low MAF). As part of this direct-2-phase II program, we propose to further develop our technology into a robust kit-based “T-Seq Solution”, comprising same day 8hr sample to sequencing, full 96-plate automated and versatile HiC protocols (to all sample types) that is compatible with existing NGS (ILMN) workflow for customer convenience and bundled with cloud-based push-button bioinformatics equipped with tools for sensitive genome-wide and targeted translocation discovery. We also propose rigorous and essential product development experiments, to ensure commercialization of a robust, premium-performance kit-based product. Upon successful completion of the technical and commercial developments in Aims 1 andamp; 2, we propose to benchmark and validate the sample-to-insight T-Seq Solution through collaboration and prototype (beta) kit and bioinformatics evaluations with key opinion leaders (KOLs) across customer segments of large sequencing centers, academic labs, and pharma.Commercialization of a highly-sensitive, scalable and low-input compatible kit-based solution for discovery of translocations from FFPE tumor biopsies Arima Genomics Project Narrative Translocations are hallmarks of Cancer. Current methods to profile translocations suffer from deficiencies of low sensitivity (WGS, Bianano), high costs (WGS, Bionano, PacBio), incompatibility to FFPE samples (SKY, Bionano, PacBio, 10X), or require direct breakpoint information (FISH and gene-panels). We have a leapfrog solution from combining FISH-type chromatin conformation capture with NGS – referred to as HiC assay with NGS sequencing (HiC-Seq). We transform the time-, labor- intensive, FFPE-incompatible and manual HiC procedure into a rapid “same day” sample to sequencing, fully automated boxed kit that handles all sample types including FFPE, fresh and frozen, and even fine needle aspirates toward high sensitivity and low cost translocation profiling. We combine the kit with push-button cloud-based informatics to enable the sample to insight T-Seq solution. Via being compatible to existing NGS workflows, our T-Seq solution offers maximum convenience, economy and sensitivity for genome-wide and targeted translocation discovery.
Tagged as:
SBIR
Phase II
2020
HHS
NIH
Commercialization of HaploSeq as a Service (HaaS) for generating chromosome-span phased genome and exome sequence information
Amount: $1,747,389 Topic: 172
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
Tagged as:
SBIR
Phase II
2018
HHS
NIH
Commercialization of a low-cost user-friendly DNA preparation kit that produces chromosome-span contiguity from conventional short-read sequencing?? for a wide range of applications
Amount: $1,776,684 Topic: 172
Commercialization of a low cost user friendly DNA preparation kit that produces chromosome span contiguity from conventional short read sequencing for a wide range of applications Arima GenomicsProject 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 areX 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 rtKbbut obtaining long gDNA fragments is challenging and this limits current SLR methodsArima Genomics has repurposed HiC technology as an SLR based DNA preparation kit that preserves chromosome span contiguity and haplotype phasing that is short read compatibleArima key technical innovation israther than using purified gDNAour method leverages the long contiguity information preserved naturally in thedimensionalDorganization of genomes in cellsasD information is long range informationBy capturingD genome informationArima s Contigo kit reconstructs chromosome span informationThe Contigo kit from Arima therefore has complete contiguity with short read economyThe Contigo kit is affordabledoes not require esoteric reagentsadditional skills or equipmentand is compatible with exiting short read workflowsto offer easy user adoptionIn additionContigo is the only kit to preserveD genomic information essential to interpreting non coding functional genomicsThe Contigo kit has the potential to serve as a new standard in next generation sequencing with broad applications in genotypingphasingallele specific gene expression and epigenetics on phased genomesstructural variation analysesmetagenomics andD genomicsIn this proposal we will commercialize the Contigo technology by improving sensitivity to wide range of cell inputs and uniformity in genome coverageand enablingwell compatibilityIn additionwe will design for manufacturereduce cost and improve sourcingassure robust performance in real world shipping and storage conditionsimprove user experienceand finallybenchmark performance of the Contigo kit with domain expertskey opinion leadersand power users to demonstrate commercial viability
Tagged as:
SBIR
Phase II
2017
HHS
NIH
Maximal resolution and full length phasing for next generation MHC typing
Amount: $274,115 Topic: NIAID
Maximal resolution and full length phasing for next generation MHC typing Arima Genomics Project Summary Abstract The Major Histocompatibility complex MHC locus is among the most polymorphic loci in the genome and harbors genes that play critical roles in human immune health and disease The polymorphic nature of the MHC locus allows for encoding every individual with a unique immune cell profile hence matching HLA genes among donors and recipients has been a critical step in mitigating immune rejections following organ transplants Advances in next generation sequencing technologies have increased the popularity of DNA sequencing as a means of typing the HLA locus for its clinical relevance Yet current HLA typing technologies ignore potentially important DNA variants type gene by gene at low resolution and fail to haplotype phase non HLA genes and other non coding alleles in the MHC locus that are necessary for optimal donor recipient matching Arima Genomics has recently developed an innovative new approach to generate full length haplotypes of the MHC locus at high resolution building on our proprietary HaploSeq technology for constructing chromosome spanning haplotypes in the human genome Our new technology andquot HaploSeq Mxandquot is capable of phasing the entire Mb HLA locus onto a single haplotype block at resolution and accuracy with just x sequencing depth As a cost effective next generation haplotyping technology HaploSeq Mx is poised to underpin a new standard in high resolution locus spanning MHC typing The objectives of Arima Genomicsandapos proposed Randamp D efforts involve improving HaploSeq Mxandapos s targeting efficiency to further reduce sequencing costs and advance the method to clinical utility developing computational approaches to improve the accuracy of HaploSeq Mx even further to andgt and demonstrating feasibility of HaploSeq Mx for MHC typing patient samples in a hematopoietic stem cell transplantation HSCT study with clinical collaborators at the Immunogenetics and Transplantation Laboratory ITL at the UCSD Center for Advanced Laboratory Medicine CALM while developing a new algorithm for donor recipient matching Successful completion of our research aims will contribute invaluable new knowledge to ongoing investigations of how human genetic variation influences patient outcomes in transplants and will substantially advance the capabilities of our HLA typing technology toward commercial viability in clinical applications HaploSeq Mx promises to greatly enhance our understanding of human genetics in health and contribute to the realization of personalized medicine Maximal resolution and full length phasing for next generation MHC typing Arima Genomics Project Narrative Determining the haplotype of the MHC locus or MHC typing is a critical step in identifying potential matches between donors and recipients for allogeneic transplants but current methods evaluate only HLA genes missing information from hundreds of other genes as well as non coding elements in this locus Consequently this can lead to potential adverse outcomes due to suboptimal MHC matching Arima Genomics recently extended our innovative HaploSeq technology as a novel cost effective approach to accurately haplotype the entire human MHC locus at high resolution to phase HLA genes non HLA genes and non coding elements in a single haplotype This new HaploSeq Mx method will enable high fidelity matching of donor and recipient for hematopoietic stem cell transplants and other allograft procedures and will contribute to a greater understanding of the human genomeandapos s role in transplant outcomes
Tagged as:
SBIR
Phase I
2016
HHS
NIH
Non-invasive determination of complete fetal genomes from cfDNA using HaploSeq
Amount: $290,577 Topic: NICHD
DESCRIPTION provided by applicant Genetic defects including single gene Mendelian disorders and aneuploidies are among the leading causes of miscarriages and congenital birth disorders Non invasive prenatal testing NIPT is currently used to detect aneuploidies but given the falling cost of next generation sequencing NGS growing sophistication in molecular biochemical methods and ever increasing computational power complete determination of the fetal genome i e genotypes and haplotypes at the level of both SNVs and large aneuploidies seems within reach In this regard cell free DNA cfDNA in the maternal plasma has been targeted for non invasive detection and diagnosis of fetal genetic defects as cfDNA contains a mixture of genetic material derived from both the mother and the fetus But because the fraction of cfDNA derived from the fetus is small and consists of DNA that is highly fragmented determination of fetal genotypes to the level of single nucleotide variants SNV remains challenging and presently involves excessively costly deep sequencing of cfDNA up to X In addition to knowledge of genotypes for diagnosing single gene Mendelian disorders non invasive deconvolution of fetal haplotypes is likely necessary for assessing the risk for complex multi genic disorders Efforts have been made to determine fetal genome with parental haplotypes but the current methods to haplotype parents generally suffer from excessive costs methodological and instrumentation complexity and or reliance on genetic material that is difficult or impossible to obtain and they provide only partial haplotype information short haplotype blocks and incomplete phasing of variants hindering their utility in cost effective complete fetal genome determination Our team previously developed an innovative approach HaploSeq that can solve this problem The HaploSeq method preserves haplotype information by preferentially recovering physically linked DNA variants on a homologous chromosome via proximity ligation and NGS as per the established HiC protocol HaploSeq achieves truly chromosome spanning haplotypes resolving the vast majority of alleles andgt at high accuracy in human genomes thus constituting the first scalable cost effective method for assembling complete human haplotypes Here we propose an innovative approach HaploSeq Ft for non invasive determination of complete fetal genotype and haplotype using HaploSeq to generate chromosome spanning parental haplotypes from blood samples In addition HaploSeqandapos s whole genome phasing capabilities also facilitate utilization of very low depth cfDNA sequencing from maternal plasma for complete fetal genotype and haplotype determination Taken together by leveraging our proprietary haplotyping technology to inform novel cfDNA sequencing analysis algorithms one HaploSeq Ft blood test will enable parents to know the complete genotype and haplotype of their fetus in a cost effective manner that does not endanger the pregnancy PUBLIC HEALTH RELEVANCE With the concurrent rise of next generation sequencing NGS technologies and non invasive prenatal testing NIPT the development of a cost effective NGS based assay that enables non invasive determination of a complete fetal genome will be essential for the future of timely diagnosis of fetal genetic disorders We propose a novel method HaploSeq Ft that leverages our proprietary haplotyping technology and new computational approaches to provide precision medicine for prenatal clinical care HaploSeq Ft will be developed as a simple non invasive cost effective blood test that enables parents to know the complete genotype and haplotype of their fetus without endangering the pregnancy
Tagged as:
SBIR
Phase I
2016
HHS
NIH
Optimizing HaploSeq for whole-genome phased haplotypes in biomedical applications
Amount: $729,686 Topic: 172
DESCRIPTION provided by applicant Phenomenal advances in DNA sequencing technologies have enabled systematic identification of genetic variants in human individuals and the recent FDA marketing authorization of the first next generation genome sequencer signals the arrival of a new era of pharmacogenomics and personalized medicine Nevertheless DNA sequencing alone fails to provide complete information on the genetic makeup of an individual as two homologous sets of chromosomes are present in the human genome Delineation of both maternal and paternal copies or haplotypes is critical for determining an individualandapos s genetic composition and for understanding the structure and function of the human genome and its role in health and disease Yet genome scale haplotyping or andquot phasingandquot of DNA variants has long remained an elusive goal Existing approaches are prohibitively expensive technically challenging require specialized instrumentation or fall far short of reconstructing chromosome spanning haplotypes Arima Genomics has recently developed an innovative new approach for whole genome haplotyping combining proximity ligation and DNA sequencing with a probabilistic algorithm for haplotype assembly This new method known as HaploSeq achieves chromosome spanning haplotypes with high completeness resolution and accuracy in mammalian genomes As a cost effective streamlined technology HaploSeq is poised to underpin a new standard in genome sequencing in biomedical applications and other markets from pharmacogenomics to agricultural biotechnology The objectives of Arima Genomicsandapos proposed Randamp D efforts involve improvement of HaploSeqandapos s ability to phase rare variants in human cells by adapting the protocol to achieve more uniform genome coverage extension of the HaploSeq algorithmandapos s capabilities to provide genotypes concurrently with haplotypes from the same source sequencing data by developing a new andquot smart mappingandquot computational module and demonstration and benchmarking of HaploSeqandapos s utility in ongoing next generation genetic association studies in partnership with clinical research collaborators at UC San Diego Successful completion of our research aims will contribute invaluable new knowledge to ongoing investigations of how human genetic variation influences the gene regulatory networks involved in cardiac biology and disease and will substantially advance the capabilities of HaploSeq toward commercial viability in diverse research biomedical and clinical sequencing applications HaploSeq promises to greatly enhance our understanding of human genetics in health and contribute to the realization of personalized medicine PUBLIC HEALTH RELEVANCE Delineating both maternal and paternal genetic copies or haplotypes is critical for determining an individualandapos s genetic composition and for understanding the structure and function of the human genome and its role in health and disease yet genome scale haplotyping or andquot phasingandquot of DNA variants has long remained an elusive goal Arima Genomics has recently developed an innovative cost effective and streamlined technology for whole genome haplotyping in humans known as HaploSeq This new method will have broad impacts in diverse research biomedical and clinical sequencing applications and promises to improve our understanding of human genetics in health and contribute to the realization of personalized medicine
Tagged as:
STTR
Phase I
2015
HHS
NIH