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Stege, U.

Publications and source records attributed to Stege, U..

2 recordsLinked to original sources

Supervised Promoter Recognition: A Benchmark Framework

AO_SCPLOWBSTRACTC_SCPLOWDeep learning has become a prevalent method in identifying genomic regulatory sequences such as promoters. In a number of recent papers, the performance of deep learning models have continually been reported as an improvement over alternatives for sequence-based promoter recognition. However, the performance improvements in these models do not account for the different datasets that models are being evaluated on. The lack of a consensus dataset and procedure for benchmarking purposes has made the comparison of each models true performance difficult to assess. We present a framework called Supervised Promoter Recognition Framework ( SUPR REF) capable of streamlining the complete process of training, validating, testing, and comparing promoter recognition models in a systematic manner. SUPR REF includes the creation of biologically relevant benchmark datasets to be used in the evaluation process of deep learning promoter recognition models. We showcase this framework by comparing the models performance on alternative datasets, and properly evaluate previously published models on new benchmark datasets. Our results show that the reliability of deep learning ab initio promoter recognition models on eukaryotic genomic sequences is still not at a sufficient level, as precision is severely lacking. Furthermore, given the observational nature of these data, cross-validation results from small datasets need to be interpreted with caution. AvailabilitySource code and documentation of the framework is available online at https://github.com/ivanpmartell/suprref

bioinformatics

SARS-CoV-2 ribosomal frameshifting pseudoknot: Improved secondary structure prediction and detection of inter-viral structural similarity

AO_SCPLOWBSTRACTC_SCPLOWSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the COVID-19 pandemic; a pandemic of a scale that has not been seen in the modern era. Despite over 29 million reported cases and over 900, 000 deaths worldwide as of September 2020, herd immunity and widespread vaccination efforts by many experts are expected to be insufficient in addressing this crisis for the foreseeable future. Thus, there is an urgent need for treatments that can lessen the effects of SARS-CoV-2 in patients who become seriously affected. Many viruses including HIV, the common cold, SARS-CoV and SARS-CoV-2 use a unique mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to successfully replicate and infect cells in the human host. SARS-CoV (the coronavirus responsible for SARS) and SARS-CoV-2 possess a unique RNA structure, a three-stemmed pseudoknot, that stimulates -1 PRF. Recent experiments identified that small molecules can be introduced as antiviral agents to bind with the pseudoknot and disrupt its stimulation of -1 PRF. If successfully developed, small molecule therapy that targets -1 PRF in SARS-CoV-2 is an excellent strategy to improve patients prognoses. Crucial to developing these successful therapies is modeling the structure of the SARS-CoV-2 -1 PRF pseudoknot. Following a structural alignment approach, we identify similarities in the -1 PRF pseudoknots of the novel coronavirus SARS-CoV-2, the original SARS-CoV, as well as a third coronavirus: MERS-CoV, the coronavirus responsible for Middle East Respiratory Syndrome (MERS). In addition, we provide a better understanding of the SARS-CoV-2 -1 PRF pseudoknot by comprehensively investigating the structural landscape using a hierarchical folding approach. Since understanding the impact of mutations is vital to long-term success of treatments that are based on predicted RNA functional structures, we provide insight on SARS-CoV-2 -1 PRF pseudoknot sequence mutations and their effect on the resulting structure and its function.

bioinformatics