Frontiers in bioinformatics最新文献

Rhizobium etli CFN42 proteome-transcriptome mixed data of exponential growth and nitrogen-fixing bacteroids, as well as Sinorhizobium meliloti 1021 transcriptome data of growth and nitrogen-fixing bacteroids, were integrated into transcriptional regulatory networks (TRNs). The one-step construction network consisted of a matrix-clustering analysis of matrices of the gene profile and all matrices of the transcription factors (TFs) of their genome. The networks were constructed with the prediction of regulatory network application of the RhizoBindingSites database (http://rhizobindingsites.ccg.unam.mx/). The deduced free-living Rhizobium etli network contained 1,146 genes, including 380 TFs and 12 sigma factors. In addition, the bacteroid R. etli CFN42 network contained 884 genes, where 364 were TFs, and 12 were sigma factors, whereas the deduced free-living Sinorhizobium meliloti 1021 network contained 643 genes, where 259 were TFs and seven were sigma factors, and the bacteroid Sinorhizobium meliloti 1021 network contained 357 genes, where 210 were TFs and six were sigma factors. The similarity of these deduced condition-dependent networks and the biological E. coli and B. subtilis independent condition networks segregates from the random Erdös-Rényi networks. Deduced networks showed a low average clustering coefficient. They were not scale-free, showing a gradually diminishing hierarchy of TFs in contrast to the hierarchy role of the sigma factor rpoD in the E. coli K12 network. For rhizobia networks, partitioning the genome in the chromosome, chromids, and plasmids, where essential genes are distributed, and the symbiotic ability that is mostly coded in plasmids, may alter the structure of these deduced condition-dependent networks. It provides potential TF gen-target relationship data for constructing regulons, which are the basic units of a TRN.

Molecular visualization is a powerful way to represent the complex structure of molecules and their higher order assemblies, as well as the dynamics of their interactions. Although conventions for depicting static molecular structures and complexes are now well established and guide the viewer's attention to specific aspects of structure and function, little attention and design classification has been devoted to how molecular motion is depicted. As we continue to probe and discover how molecules move - including their internal flexibility, conformational changes and dynamic associations with binding partners and environments - we are faced with difficult design challenges that are relevant to molecular visualizations both for the scientific community and students of cell and molecular biology. To facilitate these design decisions, we have identified twelve molecular animation design principles that are important to consider when creating molecular animations. Many of these principles pertain to misconceptions that students have primarily regarding the agency of molecules, while others are derived from visual treatments frequently observed in molecular animations that may promote misconceptions. For each principle, we have created a pair of molecular animations that exemplify the principle by depicting the same content in the presence and absence of that design approach. Although not intended to be prescriptive, we hope this set of design principles can be used by the scientific, education, and scientific visualization communities to facilitate and improve the pedagogical effectiveness of molecular animation.

Sequence alignments are often used to analyze genomic data. However, such alignments are often only calculated and compared on small sequence intervals for analysis purposes. When comparing longer sequences, these are usually divided into shorter sequence intervals for better alignment results. This usually means that the order context of the original sequence is lost. To prevent this, it is possible to use a graph structure to represent the order of the original sequence on the alignment blocks. The visualization of these graph structures can provide insights into the structural variations of genomes in a semi-global context. In this paper, we propose a new graph drawing framework for representing gMSA data. We produce a hierarchical graph layout that supports the comparative analysis of genomes. Based on a reference, the differences and similarities of the different genome orders are visualized. In this work, we present a complete graph drawing framework for gMSA graphs together with the respective algorithms for each of the steps. Additionally, we provide a prototype and an example data set for analyzing gMSA graphs. Based on this data set, we demonstrate the functionalities of the framework using two examples.

Transcription factors are essential DNA-binding proteins that regulate the transcription rate of several genes and control the expression of genes inside a cell. The prediction of transcription factors with high precision is important for understanding biological processes such as cell differentiation, intracellular signaling, and cell-cycle control. In this study, we developed a hybrid method that combines alignment-based and alignment-free methods for predicting transcription factors with higher accuracy. All models have been trained, tested, and evaluated on a large dataset that contains 19,406 transcription factors and 523,560 non-transcription factor protein sequences. To avoid biases in evaluation, the datasets were divided into training and validation/independent datasets, where 80% of the data was used for training, and the remaining 20% was used for external validation. In the case of alignment-free methods, models were developed using machine learning techniques and the composition-based features of a protein. Our best alignment-free model obtained an AUC of 0.97 on an independent dataset. In the case of the alignment-based method, we used BLAST at different cut-offs to predict the transcription factors. Although the alignment-based method demonstrated excellent performance, it was unable to cover all transcription factors due to instances of no hits. To combine the strengths of both methods, we developed a hybrid method that combines alignment-free and alignment-based methods. In the hybrid method, we added the scores of the alignment-free and alignment-based methods and achieved a maximum AUC of 0.99 on the independent dataset. The method proposed in this study performs better than existing methods. We incorporated the best models in the webserver/Python Package Index/standalone package of "TransFacPred" (https://webs.iiitd.edu.in/raghava/transfacpred).

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

Rapid advancements in high-throughput single-cell RNA-seq (scRNA-seq) technologies and experimental protocols have led to the generation of vast amounts of transcriptomic data that populates several online databases and repositories. Here, we systematically examined large-scale scRNA-seq databases, categorizing them based on their scope and purpose such as general, tissue-specific databases, disease-specific databases, cancer-focused databases, and cell type-focused databases. Next, we discuss the technical and methodological challenges associated with curating large-scale scRNA-seq databases, along with current computational solutions. We argue that understanding scRNA-seq databases, including their limitations and assumptions, is crucial for effectively utilizing this data to make robust discoveries and identify novel biological insights. Such platforms can help bridge the gap between computational and wet lab scientists through user-friendly web-based interfaces needed for democratizing access to single-cell data. These platforms would facilitate interdisciplinary research, enabling researchers from various disciplines to collaborate effectively. This review underscores the importance of leveraging computational approaches to unravel the complexities of single-cell data and offers a promising direction for future research in the field.

The major histocompatibility (MHC) locus, also known as the Human Leukocyte Antigen (HLA) genes, is located on the short arm of chromosome 6, and contains three regions (Class I, Class II and Class III). This 5 Mbp locus is one of the most variable regions of the human genome, yet it also encodes a set of highly conserved and important proteins related to immunological response. Genetic variations in this region are responsible for more diseases than in the entire rest of the human genome. However, information on local structural features of the DNA is largely ignored. With recent advances in long-read sequencing technology, it is now becoming possible to sequence the entire 5 Mbp MHC locus, producing complete diploid haplotypes of the whole region. Here, we describe structural maps based on the complete sequences from six different homozygous HLA cell lines. We find long-range structural variability in the different sequences for DNA stacking energy, position preference and curvature, variation in repeats, as well as more local changes in regions forming open chromatin structures, likely to influence gene expression levels. These structural maps can be useful in visualizing large scale structural variation across HLA types, in particular when this can be complemented with epigenetic signals.

We generalize a problem of finding maximum-scoring segment sets, previously studied by Csűrös (IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2004, 1, 139-150), from sequences to graphs. Namely, given a vertex-weighted graph G and a non-negative startup penalty c, we can find a set of vertex-disjoint paths in G with maximum total score when each path's score is its vertices' total weight minus c. We call this new problem maximum-scoring path sets (MSPS). We present an algorithm that has a linear-time complexity for graphs with a constant treewidth. Generalization from sequences to graphs allows the algorithm to be used on pangenome graphs representing several related genomes and can be seen as a common abstraction for several biological problems on pangenomes, including searching for CpG islands, ChIP-seq data analysis, analysis of region enrichment for functional elements, or simple chaining problems.

Rad And Gem-Like GTP-Binding Protein 2 (Rem2), a member of the RGK family of Ras-like GTPases, is implicated in Huntington's disease and Long QT Syndrome and is highly expressed in the brain and endocrine cells. We examine the evolutionary history of Rem2 identified in various mammalian species, focusing on the role of purifying selection and coevolution in shaping its sequence and protein structural constraints. Our analysis of Rem2 sequences across 175 mammalian species found evidence for strong purifying selection in 70% of non-invariant codon sites which is characteristic of essential proteins that play critical roles in biological processes and is consistent with Rem2's role in the regulation of neuronal development and function. We inferred epistatic effects in 50 pairs of codon sites in Rem2, some of which are predicted to have deleterious effects on human health. Additionally, we reconstructed the ancestral evolutionary history of mammalian Rem2 using protein structure prediction of extinct and extant sequences which revealed the dynamics of how substitutions that change the gene sequence of Rem2 can impact protein structure in variable regions while maintaining core functional mechanisms. By understanding the selective pressures, protein- and gene - interactions that have shaped the sequence and structure of the Rem2 protein, we gain a stronger understanding of its biological and functional constraints.

Bioinformatics, the interdisciplinary field that combines biology, computer science, and data analysis, plays a pivotal role in advancing our understanding of life sciences. In the African context, where the diversity of biological resources and healthcare challenges is substantial, fostering bioinformatics literacy and proficiency among students is important. This perspective provides an overview of the state of bioinformatics literacy among African students, highlighting the significance, challenges, and potential solutions in addressing this critical educational gap. It proposes various strategies to enhance bioinformatics literacy among African students. These include expanding educational resources, fostering collaboration between institutions, and engaging students in research projects. By addressing the current challenges and implementing comprehensive strategies, African students can harness the power of bioinformatics to contribute to innovative solutions in healthcare, agriculture, and biodiversity conservation, ultimately advancing the continent's scientific capabilities and improving the quality of life for her people. In conclusion, promoting bioinformatics literacy among African students is imperative for the continent's scientific development and advancing frontiers of biological research.