Biology subjects

Umar, I.

Publications and source records attributed to Umar, I..

3 recordsLinked to original sources

bioRxiv2022

Crowd-sourced benchmarking of single-sample tumour subclonal reconstruction

Tumours are dynamically evolving populations of cells. Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumour evolution, allowing assessment of how cancers initiate, progress and respond to selective pressures. A plethora of subclonal reconstruction algorithms have been created, but their relative performance across the varying biological and technical features of real-world cancer genomic data is unclear. We therefore launched the ICGC-TCGA DREAM Somatic Mutation Calling -- Tumour Heterogeneity and Evolution Challenge. This seven-year community effort used cloud-computing to benchmark 31 containerized subclonal reconstruction algorithms on 51 simulated tumours. Each algorithm was scored for accuracy on seven independent tasks, leading to 12,061 total runs. Algorithm choice influenced performance significantly more than tumour features, but purity-adjusted read-depth, copy number state and read mappability were associated with performance of most algorithms on most tasks. No single algorithm was a top performer for all seven tasks and existing ensemble strategies were surprisingly unable to outperform the best individual methods, highlighting a key research need. All containerized methods, evaluation code and datasets are available to support further assessment of the determinants of subclonal reconstruction accuracy and development of improved methods to understand tumour evolution.

bioinformatics↗

bioRxiv2020

A precautionary solution to estimation bias in shaping safe harvest boundaries

Biased estimates of population status are a pervasive conservation problem. This problem has plagued assessments of commercial exploitation of marine species and can threaten the sustainability of both populations and fisheries. We develop a computer-intensive approach to minimize adverse effects of persistent estimation bias in assessments by optimizing operational harvest measures (harvest control rules) with closed-loop simulation of resource-management feedback systems: management strategy evaluation. Using saithe (Pollachius virens), a bottom-water, apex predator in the North Sea, as a real-world case study, we illustrate the approach by first diagnosing robustness of the existing harvest control rule and then optimizing it through propagation of biases (overestimated stock abundance and underestimated fishing pressure) along with select process and observation uncertainties. Analyses showed that severe biases lead to overly optimistic catch limits and then progressively magnify the amplitude of catch fluctuation, thereby posing unacceptably high overharvest risks. Consistent performance of management strategies to conserve the resource can be achieved by developing more robust control rules. These rules explicitly account for estimation bias through a computational grid search for a set of control parameters (threshold abundance that triggers management action, Btrigger, and target exploitation rate, Ftarget) that maximize yield while keeping stock abundance above a precautionary level. When the biases become too severe, optimized control parameters- for saithe, raising Btrigger and lowering Ftarget-would safeguard against overharvest risk (<3.5% probability of stock depletion) and provide short-term stability in catch limit (<20% year-to-year variation), thereby minimizing disruption to fishing communities. The precautionary approach to fine-tuning adaptive risk management through management strategy evaluation offers a powerful tool to better shape sustainable harvest boundaries for exploited resource populations when estimation bias persists. By explicitly accounting for emergent sources of uncertainty our proposed approach ensures effective conservation and sustainable exploitation of living marine resources even under profound uncertainty. Open Research StatementData sets and code utilized for this research are available on Figshare. DOI: https://doi.org/10.6084/m9.figshare.13281266

ecology↗

bioRxiv2018

Creating Standards for Evaluating Tumour Subclonal Reconstruction

Tumours evolve through time and space. Computational techniques have been developed to infer their evolutionary dynamics from DNA sequencing data. A growing number of studies have used these approaches to link molecular cancer evolution to clinical progression and response to therapy. There has not yet been a systematic evaluation of methods for reconstructing tumour subclonality, in part due to the underlying mathematical and biological complexity and to difficulties in creating gold-standards. To fill this gap, we systematically elucidated the key algorithmic problems in subclonal reconstruction and developed mathematically valid quantitative metrics for evaluating them. We then created approaches to simulate realistic tumour genomes, harbouring all known mutation types and processes both clonally and subclonally. We then simulated 580 tumour genomes for reconstruction, varying tumour read-depth and benchmarking somatic variant detection and subclonal reconstruction strategies. The inference of tumour phylogenies is rapidly becoming standard practice in cancer genome analysis; this study creates a baseline for its evaluation.

bioinformatics↗