Dataset Information

Unsupervised and Supervised Learning over theEnergy Landscape for Protein Decoy Selection.

ABSTRACT: The energy landscape that organizes microstates of a molecular system and governs theunderlying molecular dynamics exposes the relationship between molecular form/structure, changesto form, and biological activity or function in the cell. However, several challenges stand in the wayof leveraging energy landscapes for relating structure and structural dynamics to function. Energylandscapes are high-dimensional, multi-modal, and often overly-rugged. Deep wells or basins inthem do not always correspond to stable structural states but are instead the result of inherentinaccuracies in semi-empirical molecular energy functions. Due to these challenges, energeticsis typically ignored in computational approaches addressing long-standing central questions incomputational biology, such as protein decoy selection. In the latter, the goal is to determine over apossibly large number of computationally-generated three-dimensional structures of a protein thosestructures that are biologically-active/native. In recent work, we have recast our attention on theprotein energy landscape and its role in helping us to advance decoy selection. Here, we summarizesome of our successes so far in this direction via unsupervised learning. More importantly, we furtheradvance the argument that the energy landscape holds valuable information to aid and advance thestate of protein decoy selection via novel machine learning methodologies that leverage supervisedlearning. Our focus in this article is on decoy selection for the purpose of a rigorous, quantitativeevaluation of how leveraging protein energy landscapes advances an important problem in proteinmodeling. However, the ideas and concepts presented here are generally useful to make discoveriesin studies aiming to relate molecular structure and structural dynamics to function.

SUBMITTER: Akhter N

PROVIDER: S-EPMC6843838 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Unsupervised and Supervised Learning over theEnergy Landscape for Protein Decoy Selection.

Akhter Nasrin N Chennupati Gopinath G Kabir Kazi Lutful KL Djidjev Hristo H Shehu Amarda A

Biomolecules 20191014 10

The energy landscape that organizes microstates of a molecular system and governs theunderlying molecular dynamics exposes the relationship between molecular form/structure, changesto form, and biological activity or function in the cell. However, several challenges stand in the wayof leveraging energy landscapes for relating structure and structural dynamics to function. Energylandscapes are high-dimensional, multi-modal, and often overly-rugged. Deep wells or basins inthem do not always corres ...[more]

PMID: 31615116

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Project description:This work aimed to identify pre-existing health conditions of patients with traumatic brain injury (TBI) and develop predictive models for the first TBI event and its external causes by employing a combination of unsupervised and supervised learning algorithms. We acquired up to five years of pre-injury diagnoses for 488,107 patients with TBI and 488,107 matched control patients who entered the emergency department or acute care hospitals between April 1st, 2002, and March 31st, 2020. Diagnoses were obtained from the Ontario Health Insurance Plan (OHIP) database which contains province-wide claims data by physicians in Ontario, Canada for inpatient and outpatient services. A screening process was conducted on the OHIP diagnostic codes to limit the subsequent analysis to codes that were predictive of TBI, which concluded that 314 codes were significantly associated with TBI. The Latent Dirichlet Allocation (LDA) model was applied to the diagnostic codes and generated an optimal number of 19 topics that concur with published literature but also suggest other unexplored areas. Estimated word-topic probabilities from the LDA model helped us detect pre-morbid conditions among patients with TBI by uncovering the underlying patterns of diagnoses, meanwhile estimated document-topic probabilities were utilized in variable creation as form of a dimension reduction. We created 19 topic scores for each patient in the cohort which were utilized along with socio-demographic factors for Random Forest binary classifier models. Test set performances evaluated using area under the receiver operating characteristic curve (AUC) were: TBI event (AUC = 0.85), external cause of injury: falls (AUC = 0.85), struck by/against (AUC = 0.83), cyclist collision (AUC = 0.76), motor vehicle collision (AUC = 0.83). Our analysis successfully demonstrated the feasibility of using machine learning to predict TBI due to various external causes and identified the most important factors that contribute to this prediction.

Dataset Information

Unsupervised and Supervised Learning over theEnergy Landscape for Protein Decoy Selection.

Publications

Unsupervised and Supervised Learning over theEnergy Landscape for Protein Decoy Selection.

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