Abbreviated Name

Lung Ref Set B App: Adams (2021)

Lead Investigator

Adams, Eddie — Micronoma, Inc.

Coordinating Investigator

Zheng, Yingye — Fred Hutchinson Cancer Center

Involved Investigators

• Adams, Eddie — Micronoma, Inc.
• Zheng, Yingye — Fred Hutchinson Cancer Center

Abstract

Abstract: Micronoma is developing a liquid biopsy, plasma-based diagnostic test (Oncobiota™Lung Assay) that utilizes the detection of cancer-associated microbial DNA signatures to provide a lung cancer probably score. It is intended to be used in patients ≥ 50 years old after a positive low-dose CT (LDCT) screening test as an aid to assess the likelihood that a radiologically detected lung nodule is malignant when independent clinical and radiometric evaluations alone do not indicate malignancy. The assay will also be employed to address the nodule status of patients with incidentally determined lung nodules undergoing evaluation for other, non-cancer pulmonary conditions (e.g., sarcoidosis, COPD, interstitial pulmonary fibrosis). The test is not intended as a screening or stand-alone diagnostic assay. Given the focus of our assay—clinical triage of LDCT-detected pulmonary nodules—EDRN Lung Cancer Reference Set B represent an ideal independent test set with which we can validate the performance of our optimized liquid biopsy assay.

Aims

Specific Aims: I.   Isolate total cell-free DNA from the EDRN Lung Cancer Reference Set B plasma samples and generate next generation sequencing quality libraries. II.   Sequence the NGS libraries from (I.) and process the sequencing reads through our metagenomics computational pipeline to identify circulating microbial DNA sequences and their taxonomic abundance. III.   Use our trained and tuned machine learning model to analyze and predict the lung cancer status of the samples based on the sequencing data in (II.).

Analytic Method

The Oncobiota™Lung Assay utilizes shotgun metagenomic sequencing of patient samples at a target read depth of 20 million reads/sample, a sequencing depth commonly employed in cfDNA copy number variation analyses and shallow whole genome sequencing analyses of somatic mutations. Sequencing in this manner (i.e., non-targeted) gives us access to all taxonomic sources of DNA fragments in circulation (human, bacterial, fungal, viral, and archaeal) and enables the discovery and downstream employment of complex, multi-analyte diagnostic signatures. Total cell-free DNA (human and non-human DNA) is isolated from 400 microliters of K2- or K3-EDTA plasma alongside DNA extraction (blank) controls and used to prepare libraries for Illumina sequencing. Raw sequencing reads are mapped to the human genome and all non-human reads (nominally of microbial origin, are processed through our decontamination metagenomics pipeline to remove historically common DNA extraction kit microbial contaminants and any contaminants identified in DNA extraction controls. The filtered remaining reads are taxonomically assigned using a proprietary workflow against a microbial genome database containing all complete refseq genomes from viruses, bacteria, fungi, and archaea. Feature tables consisting of assigned taxa and their associated abundances are inputted into a trained and tuned machine learning model for analysis and generation of a cancer probability score.

Outcome

Abstract: Micronoma is developing a liquid biopsy, plasma-based diagnostic test (Oncobiota™Lung Assay) that utilizes the detection of cancer-associated microbial DNA signatures to provide a lung cancer probably score. It is intended to be used in patients ≥ 50 years old after a positive low-dose CT (LDCT) screening test as an aid to assess the likelihood that a radiologically detected lung nodule is malignant when independent clinical and radiometric evaluations alone do not indicate malignancy. The assay will also be employed to address the nodule status of patients with incidentally determined lung nodules undergoing evaluation for other, non-cancer pulmonary conditions (e.g., sarcoidosis, COPD, interstitial pulmonary fibrosis). The test is not intended as a screening or stand-alone diagnostic assay. Given the focus of our assay—clinical triage of LDCT-detected pulmonary nodules—EDRN Lung Cancer Reference Set B represent an ideal independent test set with which we can validate the performance of our optimized liquid biopsy assay.

Publications

• No publications available at this time for this protocol.

Biomarkers

• No biomarkers available at this time for this protocol.

Data Collections

• No data collections available at this time for this protocol.

 Team Project

Start Date

Jan 1 2022

Estimated Finish Date

Jan 1 2023

Finish Date

Feb 8 2023

Protocol ID

502

Protocol Type

Reference Set

Fields of Research

• UNKNOWN

Collaborative Group

Lung and Upper Aerodigestive Cancers Research Group

Cancer Types

• Malignant neoplasm of bronchus and lung