Genome sequencing technology has been transformative in the analysis of cancer. From genomic, transcriptomic,andepigeneticdata,researchersaremakingnewdiscoveriesaboutthemechanismsofcancer developmentthat are leading tonew therapiesanddiagnostic tests. Accelerating these discoveries,genomic analysisisbeingappliedtoawidevarietyofanalytessuchascell-freeDNAandsinglecellsfromtissuebiopsies. However, given the increasing range ofavailable genomic sequencing assays available for cancer genomic studies, a major challenge comes from the limited amounts of clinical tumor samples. Tissue biopsies and samplesoftentimesprovideasmallamountofgenomicanalyte.Asaresult,onlyoneortwogenomicsequencing experimentscanbeperformed,whichleadstoalessthancompletepictureoffeaturesofapatienttumor. Toaddressthisissue,wedevelopedandvalidatedatechnologycalledAPEX?thissequencingtechnology enablesrepeateduseofthesame nucleicacidanalytesderivedfromavarietyofclinicalsamplesrelevantfor cancertranslationalresearchandclinicalstudies.Asaresult,researchershavetheopportunitytoconductmany types of genomic analyses on the same sample and genomic material. APEX technology is based on the covalent attachment of nucleic acid analytes to a solid support, so that the original genomic material is permanentlyretained,canbesubjecttoavarietyofsequencingassaysandasaresult,canbeanalyzedthrough manyiterations.Theuseofmultipleiterationsalsooffersanopportunitytoimprovethedelineationsofcritical genomicaberrationsthatoccurinonlyasmallfractionofthetumorcells.WeproposethedevelopmentofAPEX for integrated multi-modal and iterative genomic analyses of primary cancer biopsies and cell free DNA from patients.
Aim1 focusesoncell-freeDNAanalytes,andAim2focusesonsingle-celltranscriptomesequencing. Overall, our proposed APEX technology will broadly impact the field of translational cancer research by providinganewplatformwherebyclinicalsamplescanbeusedasarenewableresourceforsubsequentgenomic sequencing. It removes constraints afforded by limited amountsof tissue samples from translational clinical studies.Withtheseimprovements,APEXwillimprovetheassessmentofsomaticgenomicalterationsincancer cells, integration of multi-modal sequencingtechnologies,and offerpersonalized molecular analyses for each cancerpatient.
Genomic sequencing technologies have rapidly emerged to enable the identification of markers that can diagnose cancers, identify potential targeted therapies, and predict outcomes for cancer patients. However, tiny amounts of available biopsy material limit the types of genomic analyses that can be performed. Our project solves this limitation by the development of a technology that enables material from clinical biopsies to be used repeatedly without loss, enabling a wide breadth of sequencing analyses can be performed on a patient?s cancer with more accurate results.
