Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300× compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables plasma-only (non-tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune-checkpoint inhibition.

Community implications for gun violence prevention during co-occurring pandemics; a qualitative and computational analysis study.

This study provides insight into New York City residents' perceptions about violence after the outbreak of Coronavirus disease (COVID-19) based on information from communities in New York City Housing Authority (NYCHA) buildings. In this novel analysis, we used focus group and social media data to confirm or reject findings from qualitative interviews. We first used data from 69 in-depth, semi-structured interviews with low-income residents and community stakeholders to further explore how violence impacts New York City's low-income residents of color, as well as the role of city government in providing tangible support for violence prevention during co-occurring health (COVID-19) and social (anti-Black racism) pandemics. Residents described how COVID-19 and the Black Lives Matter movement impacted safety in their communities while offering direct recommendations to improve safety. Residents also shared recommendations that indirectly improve community safety by addressing long term systemic issues. As the recruitment of interviewees was concluding, researchers facilitated two focus groups with 38 interviewees to discuss similar topics. In order to assess the degree to which the themes discovered in our qualitative interviews were shared by the broader community, we developed an integrative community data science study which leveraged natural language processing and computer vision techniques to study text and images on public social media data of 12 million tweets generated by residents. We joined computational methods with qualitative analysis through a social work lens and design justice principles to most accurately and holistically analyze the community perceptions of gun violence issues and potential prevention strategies. Findings indicate valuable community-based insights that elucidate how the co-occurring pandemics impact residents' experiences of gun violence and provide important implications for gun violence prevention in a digital era.