Unifying package managers, workflow engines, and containers: Computational reproducibility with BioNix

Bedő, Justin; Stefano, Leon Di; Papenfuss, Anthony T.

doi:10.1093/gigascience/giaa121

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…To our opinion, the main difference between the Guix and Nix systems is, for the former a continuity from the high-level declarative configuration to the core which allows to adapt or extend the Guix system, and for the latter, on one hand “Nix expressions” written in a DSL specifically designed to define these “pure functions” (derivation), and on the other hand another language for the core. This difference is slight in practice but emphasized by the data processing workflow engines Guix Workflow Language (GWL) based on Guix and BioNix 22 based on Nix ( https://youtu.be/pwYhPqaUiGg , https://youtu.be/tpLcwfRXL28 ). Last, to our knowledge, the Nix system does not provide yet a mechanism easing the time travel.…”

Section: Resultsmentioning

confidence: 99%

“…To be fully reproducible one computational environment must be defined by (i) the source code of the software and libraries used (ii) the various options or configuration are required at build-time or run-time and (iii) the complete graph that fixes all the dependencies. Package manager like Nix 22 and Guix are designed around these three requirements. By using Nix or Guix, scientists are now able to easily share their computational environment.…”

Section: Discussionmentioning

confidence: 99%

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Toward practical transparent verifiable and long-term reproducible research using Guix

2022

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Reproducibility crisis urge scientists to promote transparency which allows peers to draw same conclusions after performing identical steps from hypothesis to results. Growing resources are developed to open the access to methods, data and source codes. Still, the computational environment, an interface between data and source code running analyses, is not addressed. Environments are usually described with software and library names associated with version labels or provided as an opaque container image. This is not enough to describe the complexity of the dependencies on which they rely to operate on. We describe this issue and illustrate how open tools like Guix can be used by any scientist to share their environment and allow peers to reproduce it. Some steps of research might not be fully reproducible, but at least, transparency for computation is technically addressable. These tools should be considered by scientists willing to promote transparency and open science.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Toward practical transparent verifiable and long-term reproducible research using Guix

2022

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“…A bionix (57) pipeline was used to process samples from sequencing data to variant calls. Sequences were aligned to Genome Reference Consortium Human Build 38 (GRCh38) using minimap2 v2.17 (58), and also to Mus Musculus reference GRCm38.…”

Section: Methodsmentioning

confidence: 99%

BRCA1secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance

Nesic

Krais

Vandenberg

et al. 2023

Preprint

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BRCA1 splice isoforms Δ11 and Δ11q can contribute to PARP inhibitor (PARPi) resistance by splicing-out mutation-containing exons, producing truncated, partially-functional proteins. However, the clinical impact and underlying drivers of BRCA1 exon skipping remain undetermined. We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for splice isoform expression and therapy response. This included a matched PDX pair derived from a patient pre- and post-chemotherapy/PARPi regimen. BRCA1 exon 11-deficient isoform expression was generally elevated in PARPi resistant PDX tumors. Two independent PDX models acquired secondary BRCA1 splice site mutations (SSMs), predicted in silico to drive exon skipping. Predictions were confirmed using qRT-PCR, RNA sequencing, western blots and BRCA1 minigene modelling. SSMs were also enriched in post-PARPi OC patient cohorts from the ARIEL2 and ARIEL4 clinical trials. We demonstrate that SSMs drive BRCA1 exon 11 skipping and PARPi resistance, and should be clinically monitored, along with frame-restoring secondary mutations.

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“…A bionix 47 pipeline was used to process samples from sequencing data to variant calls. Sequences were aligned to Genome Reference Consortium Human Build 38 (GRCh38) using minimap2 v2.17, 48 and also to the Mus Musculus reference GRCm38 for PDX.…”

Section: Genome Sequencing Analysismentioning

confidence: 99%

The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models

Ho,

Vandenberg,

Lim

et al. 2023

Ther Adv Med Oncol

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Background: Despite initial response to platinum-based chemotherapy and PARP inhibitor therapy (PARPi), nearly all recurrent high-grade serous ovarian cancer (HGSC) will acquire lethal drug resistance; indeed, ~15% of individuals have de novo platinum-refractory disease. Objectives: To determine the potential of anti-microtubule agent (AMA) therapy (paclitaxel, vinorelbine and eribulin) in platinum-resistant or refractory (PRR) HGSC by assessing response in patient-derived xenograft (PDX) models of HGSC. Design and methods: Of 13 PRR HGSC PDX, six were primary PRR, derived from chemotherapy-naïve samples (one was BRCA2 mutant) and seven were from samples obtained following chemotherapy treatment in the clinic (five were mutant for either BRCA1 or BRCA2 ( BRCA1/2), four with prior PARPi exposure), recapitulating the population of individuals with aggressive treatment-resistant HGSC in the clinic. Molecular analyses and in vivo treatment studies were undertaken. Results: Seven out of thirteen PRR PDX (54%) were sensitive to treatment with the AMA, eribulin (time to progressive disease (PD) ⩾100 days from the start of treatment) and 11 out of 13 PDX (85%) derived significant benefit from eribulin [time to harvest (TTH) for each PDX with p < 0.002]. In 5 out of 10 platinum-refractory HGSC PDX (50%) and one out of three platinum-resistant PDX (33%), eribulin was more efficacious than was cisplatin, with longer time to PD and significantly extended TTH (each PDX p < 0.02). Furthermore, four of these models were extremely sensitive to all three AMA tested, maintaining response until the end of the experiment (120d post-treatment start). Despite harbouring secondary BRCA2 mutations, two BRCA2-mutant PDX models derived from heavily pre-treated individuals were sensitive to AMA. PRR HGSC PDX models showing greater sensitivity to AMA had high proliferative indices and oncogene expression. Two PDX models, both with prior chemotherapy and/or PARPi exposure, were refractory to all AMA, one of which harboured the SLC25A40-ABCB1 fusion, known to upregulate drug efflux via MDR1. Conclusion: The efficacy observed for eribulin in PRR HGSC PDX was similar to that observed for paclitaxel, which transformed ovarian cancer clinical practice. Eribulin is therefore worthy of further consideration in clinical trials, particularly in ovarian carcinoma with early failure of carboplatin/paclitaxel chemotherapy.

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Unifying package managers, workflow engines, and containers: Computational reproducibility with BioNix

Cited by 7 publications

References 26 publications

Toward practical transparent verifiable and long-term reproducible research using Guix

Toward practical transparent verifiable and long-term reproducible research using Guix

BRCA1secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance

The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models

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