Publications by authors named "Tijana MilenkoviC"

Synonymous codons were originally viewed as interchangeable, with no phenotypic consequences. However, substantial evidence has now demonstrated that synonymous substitutions can perturb a variety of gene expression and protein homeostasis mechanisms, including translational efficiency, translational fidelity, and cotranslational folding of the encoded protein. To date, most studies of synonymous codon-derived perturbations have focused on effects within a single gene.

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Article Synopsis
  • Network biology is an interdisciplinary field that combines computational and biological sciences to improve understanding of cellular functions and diseases, though it is still a developing area after two decades.* -
  • The field faces challenges due to the increasing complexity and diversity of biological data, but active research areas include molecular networks, patient similarity networks, and machine learning applications.* -
  • The article provides an overview of recent advancements, highlights future directions, and emphasizes the need for diverse scientific communities and educational initiatives within network biology.*
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Article Synopsis
  • Malaria causes over 550,000 deaths yearly, partly due to drug-resistant genes; many genes in the malaria genome remain functionally unknown, which hinders drug target identification.
  • This study analyzes gene co-expression networks using various inference methods to improve functional annotations and validate genes, revealing high precision yet low recall in predicted annotations.
  • The networks provide complementary insights into gene interactions, with unique edges, and offer ranked lists of gene interactions and predicted annotations for future research in malaria treatment.
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Motivation: Identification of human genes involved in the aging process is critical due to the incidence of many diseases with age. A state-of-the-art approach for this purpose infers a weighted dynamic aging-specific subnetwork by mapping gene expression (GE) levels at different ages onto the protein-protein interaction network (PPIN). Then, it analyzes this subnetwork in a supervised manner by training a predictive model to learn how network topologies of known aging- versus non-aging-related genes change across ages.

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Protein structural classification (PSC) is a supervised problem of assigning proteins into pre-defined structural (e.g., CATH or SCOPe) classes based on the proteins' sequence or 3D structural features.

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Motivation: Prediction of node and graph labels are prominent network science tasks. Data analyzed in these tasks are sometimes related: entities represented by nodes in a higher-level (higher scale) network can themselves be modeled as networks at a lower level. We argue that systems involving such entities should be integrated with a 'network of networks' (NoNs) representation.

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There is a growing appreciation that synonymous codon usage, although historically regarded as phenotypically silent, can instead alter a wide range of mechanisms related to functional protein production, a term we use here to describe the net effect of transcription (mRNA synthesis), mRNA half-life, translation (protein synthesis) and the probability of a protein folding correctly to its active, functional structure. In particular, recent discoveries have highlighted the important role that sub-optimal codons can play in modifying co-translational protein folding. These results have drawn increased attention to the patterns of synonymous codon usage within coding sequences, particularly in light of the discovery that these patterns can be conserved across evolution for homologous proteins.

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Background: This study focuses on the task of supervised prediction of aging-related genes from -omics data. Unlike gene expression methods for this task that capture aging-specific information but ignore interactions between genes (i.e.

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Human aging is linked to many prevalent diseases. The aging process is highly influenced by genetic factors. Hence, it is important to identify human aging-related genes.

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Background: Network alignment (NA) can transfer functional knowledge between species' conserved biological network regions. Traditional NA assumes that it is topological similarity (isomorphic-like matching) between network regions that corresponds to the regions' functional relatedness. However, we recently found that functionally unrelated proteins are as topologically similar as functionally related proteins.

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Gene expression (GE)data capture valuable condition-specific information ("condition" can mean a biological process, disease stage, age, patient, etc.)However, GE analyses ignore physical interactions between gene products, i.e.

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Experimental determination of protein function is resource-consuming. As an alternative, computational prediction of protein function has received attention. In this context, protein structural classification (PSC) can help, by allowing for determining structural classes of currently unclassified proteins based on their features, and then relying on the fact that proteins with similar structures have similar functions.

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In this study, we deal with the problem of biological network alignment (NA), which aims to find a node mapping between species' molecular networks that uncovers similar network regions, thus allowing for the transfer of functional knowledge between the aligned nodes. We provide evidence that current NA methods, which assume that topologically similar nodes (i.e.

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Motivation: Most amino acids are encoded by multiple synonymous codons, some of which are used more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can impact co-translational protein folding and that positions of some rare codons are evolutionarily conserved. Analyses of their positions in protein 3-dimensional structures, which are richer in biochemical information than sequences alone, might further explain the role of rare codons in protein folding.

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Improved computational modeling of protein translation rates, including better prediction of where translational slowdowns along an mRNA sequence may occur, is critical for understanding co-translational folding. Because codons within a synonymous codon group are translated at different rates, many computational translation models rely on analyzing synonymous codons. Some models rely on genome-wide codon usage bias (CUB), believing that globally rare and common codons are the most informative of slow and fast translation, respectively.

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Networks are largely used for modelling and analysing a wide range of biological data. As a consequence, many different research efforts have resulted in the introduction of a large number of algorithms for analysis and comparison of networks. Many of these algorithms can deal with networks with a single class of nodes and edges, also referred to as homogeneous networks.

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Biological network alignment (NA) aims to identify similar regions between molecular networks of different species. NA can be local or global. Just as the recent trend in the NA field, we also focus on global NA, which can be pairwise (PNA) and multiple (MNA).

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Precision medicine has received attention both in and outside the clinic. We focus on the latter, by exploiting the relationship between individuals' social interactions and their mental health to predict one's likelihood of being depressed or anxious from rich dynamic social network data. Existing studies differ from our work in at least one aspect: they do not model social interaction data as a network; they do so but analyze static network data; they examine "correlation" between social networks and health but without making any predictions; or they study other individual traits but not mental health.

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Motivation: Network alignment (NA) finds conserved regions between two networks. NA methods optimize node conservation (NC) and edge conservation. Dynamic graphlet degree vectors are a state-of-the-art dynamic NC measure, used within the fastest and most accurate NA method for temporal networks: DynaWAVE.

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Understanding the relationship between individuals' social networks and health could help devise public health interventions for reducing incidence of unhealthy behaviors or increasing prevalence of healthy ones. In this context, we explore the co-evolution of individuals' social network positions and physical activities. We are able to do so because the NetHealth study at the University of Notre Dame has generated both high-resolution longitudinal social network (e.

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Network alignment (NA) compares networks with the goal of finding a node mapping that uncovers highly similar (conserved) network regions. Existing NA methods are homogeneous, i.e.

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Network clustering is a very popular topic in the network science field. Its goal is to divide (partition) the network into groups (clusters or communities) of "topologically related" nodes, where the resulting topology-based clusters are expected to "correlate" well with node label information, i.e.

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Motivation: Network alignment (NA) aims to find similar (conserved) regions between networks, such as cellular networks of different species. Until recently, existing methods were limited to aligning static networks. However, real-world systems, including cellular functioning, are dynamic.

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