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Reid, B. J.

Publications and source records attributed to Reid, B. J..

3 recordsLinked to original sources

Reconciling land sharing and sparing: a conceptual model for land use

Since the introduction of the terms in the early 2000s, the land sharing versus land sparing dichotomy has sparked considerable discussion stemming from the relationship between food production and ecological function. The theory underpinning these approaches straddles disciplinary and ideological boundaries and is frequently outlined within a general economy versus ecology background. Both strategies have come up with competing models on the relationship linking agricultural production and ecological function. The present work introduces a conceptual synthesis to unify alternative models under a single coherent framework. A generalized model linking agricultural production with ecological function that can harmonize these conflicting views is presented. In addition, a conceptual shift of paradigm is suggested to approach the issue, moving from yield targets to preservation thresholds. This article provides the theoretical means to identify the environmental and policy conditions under which land sharing strategies, based on low inputs and low impact per unit of cultivated land, can compete with land sparing approaches for the combined goals of biodiversity preservation and food safety.

ecology↗

Extrachromosomal DNA in the cancerous transformation of Barrett's esophagus

BACKGROUNDOncogenes are commonly amplified on extrachromosomal DNA (ecDNA) contributing to poor outcomes for patients. Currently, the chronology of ecDNA development is not known. We studied the origination and evolution of ecDNA in patients with Barretts esophagus (BE) who progressed to esophageal adenocarcinoma (EAC). METHODSWe analyzed whole-genome sequencing (WGS) data from a BE surveillance cohort and EAC patients at Cambridge University UK (n=206 patients). We also analyzed WGS data from biopsies taken at two time points from multiple sites in the esophagus from 80 patients enrolled in a case-control study at the Fred Hutchinson Cancer Center (FHCC) - 40 BE patients who progressed to EAC and 40 who did not. RESULTSecDNA was detected in 24% and 43% of BE patients with BE-associated early and late-stage EAC, respectively, in the Cambridge cross-sectional cohort. ecDNA was found in 33% of all FHCC BE patients who developed cancer, either prior to, or at EAC diagnosis. ecDNA was strongly associated with patients who developed cancer, in contrast with FHCC BE patients who did not progress (odds ratio, 18.8, CI - 2.3-152, p=3.3x10-4). ecDNAs were enriched for oncogenes and immunomodulatory genes and could be detected early in the transition from high-grade dysplasia to cancer and increased in copy number and complexity over time. CONCLUSIONSecDNAs can develop before a diagnosis of cancer in BE patients and are strongly selected for during the evolution to EAC. ecDNAs promote diverse oncogene and immunomodulatory gene amplification during EAC development and progression.

genomics↗

Novel patterns of complex structural variation revealed across thousands of cancer genome graphs

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g. deletion, translocation) or complex (e.g. chromothripsis, chromoplexy) structural variant classes. Applying a novel genome graph computational paradigm to analyze the topology of junction copy number (JCN) across 2,833 tumor whole genome sequences (WGS), we introduce three complex rearrangement phenomena: pyrgo, rigma, and tyfonas. Pyrgo are "towers" of low-JCN duplications associated with early replicating regions and superenhancers, and are enriched in breast and ovarian cancers. Rigma comprise "chasms" of low-JCN deletions at late-replicating fragile sites in esophageal and other gastrointestinal (GI) adenocarcinomas. Tyfonas are "typhoons" of high-JCN junctions and fold back inversions that are enriched in acral but not cutaneous melanoma and associated with a previously uncharacterized mutational process of non-APOBEC kataegis. Clustering of tumors according to genome graph-derived features identifies subgroups associated with DNA repair defects and poor prognosis.

genomics↗