Development of A Digital Pathology Database for Annotation and Quality Management of a Brain Tumor Biorepository Jeremy Molligan, MD Pathology

How do we integrate and utilize all of this information? Information Age Collecting terabytes of information per patient Next Generation Assays Personalized Medicine Iniatives Intelligent Biosensors Investments in Basic, Clinical, & Translational Research How do we integrate and utilize all of this information?

Objectives Establish a CAP accredited, quality-controlled tissue bank for neuro-oncologic research Integration of Informatics Clinical, Radiology, Histopathology, Genomics Platform for Translational Research

Tissue Specimens Collection directly from OR Warm-ischemia Time < 5 min Cold-ischemia Time < 15 min SNAP Frozen RNAlater - Nucleic Acids FFPE with QC Slide

Direct collection from OR Specimen Work Flow Direct collection from OR Aliquot 10% Formalin for FFPE RNAlater SNAP Frozen Quality Control Molecular Analysis Research

Blood Specimens PAXGene tubes Immediate RNA & DNA stabilization Kits for high-throughput processing EDTA tubes Standard Plasma, Buffy-coat

Quality Control 5-10% Sampling Audit Nucleic Acids Nanodrop: A260/280 Aigilent TapeStation: RIN (Digital Electrophoresis) FFPE Slide verified by attending Neuropathologist SPREC - Documentation of Pre- analytic Variables (cold-ischemia time, thaws, centrifuge speed)

RFID-based Tracking BioTillion - RFID Bioinventory Management System Software integration with OpenSpecimen Reduces cataloging errors

Data Capture NEURO DB LIS OPEN SPECIMEN ELECTRONIC MEDICAL RECORD Clinical and demographic information is gathered for diagnostic and therapeutic purposes NEURO DB Clinical research paramteres are captured prospectively and retrospectively LIS Anatomic Pathology Laboratory Information System OPEN SPECIMEN Biospecimen information and clinical annotation

Neuro DB Security - Password-protected, user management system, Jefferson Firewall Accessible - Any computer on Jefferson Campus, No software downloads Customizable - Forms can be tailored to specific research interests Fidelity - Designed to limit erroneous user input; Intuitive User Interface Integrated - Link clinical data to biospecimens

Neuro DB

Neuro DB

OpenSpecimen OpenSpecimen - Bioinventory Management System Open source web application SQL Backend Custom work flows REST API

OpenSpecimen

Digital Pathology Leica Aperio – High resolution, whole slide image capture OpenSeadragon – Open source, web-based WSI viewer Directly integrated into biorepository LIS WYSIWYG for researchers Infrastructure for future analytics: AI & Machine Vision Analysis

Data Work Flow NEURO DB I2B2 OPEN SPECIMEN APERIO EMR LIS Clinical research data capture I2B2 Data Integration Biorepository specimen data capture OPEN SPECIMEN APERIO Whole Slide Imaging (Digital Pathology) EMR Clinical Information LIS Anatomic Pathology Information System

i2b2 i2b2- Web-based Query & Analysis Tool Data Aggregation Integration of Clinical, Pathologic, Genomic, & Biospecimen Data

i2b2

Current Collected 250+ Cranial Base Neurologic Cases Benign, Malignant, and Metastasis >2500 individual specimens Seven Neurosurgery & ENT surgeons Pending CAP inspection & approval

Summary Established a quality controlled digital pathology system for our brain tumor biorepository Integrated clinical, pathologic, and genomic information systems Serves as foundation for current and future translational research iniatives