PaperPlayer biorxiv bioinformatics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.23.218800v1?rss=1

Authors: He, J., Babarinde, I. A., Sun, L., Xu, S., Chen, R., Wei, Y., Li, Y., Ma, G., Zhuang, Q., Hutchins, A., Chen, J.

Abstract:

Transposable elements (TEs) make up a majority of a typical eukaryote's genome, and contribute to cell heterogeneity and fate in unclear ways. Single cell-sequencing technologies are powerful tools to explore cells, however analysis is typically gene-centric and TE activity has not been addressed. Here, we developed a single-cell TE processing pipeline, scTE, and report the activity of TEs in single cells in a range of biological contexts. Specific TE types were expressed in subpopulations of embryonic stem cells and were dynamically regulated during pluripotency reprogramming, differentiation, and embryogenesis. Unexpectedly, TEs were expressed in somatic cells, including human disease-specific TEs that are undetectable in bulk analyses. Finally, we applied scTE to single cell ATAC-seq data, and demonstrate that scTE can discriminate cell type using chromatin accessibly of TEs alone. Overall, our results reveal the dynamic patterns of TEs in single cells and their contributions to cell fate and heterogeneity.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.24.219097v1?rss=1

Authors: Acera Mateos, P., Balboa, R. F., Easteal, S., Eyras, E., Patel, H. R.

Abstract:

Viral co-infections occur in COVID-19 patients, potentially impacting disease progression and severity. However, there is currently no dedicated method to identify viral co-infections in patient RNA-seq data. We developed PACIFIC, a deep-learning algorithm that accurately detects SARS-CoV-2 and other common RNA respiratory viruses from RNA-seq data. Using in silico data, PACIFIC recovers the presence and relative concentrations of viruses with >99% precision and recall. PACIFIC accurately detects SARS-CoV-2 and other viral infections in 63 independent in vitro cell culture and patient datasets. PACIFIC is an end-to-end tool that enables the systematic monitoring of viral infections in the current global pandemic.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.22.216242v1?rss=1

Authors: Vitanyi, P. M. B., Cilibrasi, R. L.

Abstract:

We analyze the phylogeny and taxonomy of the SARS-CoV-2 virus using compression. This is a new alignment-free method called the "normalized compression distance" (NCD) method. It discovers all effective similarities based on Kolmogorov complexity. The latter being incomputable we approximate it by a good compressor such as the modern zpaq. The results comprise that the SARS-CoV-2 virus is closest to the RaTG13 virus and similar to two bat SARS-like coronaviruses bat-SL-CoVZXC21 and bat-SL-CoVZC4. The similarity is quantified and compared with the same quantified similarities among the mtDNA of certain species. We treat the question whether Pangolins are involved in the SARS-CoV-2 virus.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.22.214262v1?rss=1

Authors: Shiraishi, Y., Koya, J., Chiba, K., Saito, Y., Okada, A., Kataoka, K.

Abstract:

We introduce our novel software, nanomonsv, for detecting somatic structural variations (SVs) using tumor and matched control long-read sequencing data with a single-base resolution. Using paired long-read sequencing data from three cancer cell-lines and their matched lymphoblastoid lines, we demonstrate that our approach can identify not only somatic SVs that can be captured with short-read technologies but also novel ones especially those whose breakpoints are located in repeat regions. In addition, we have developed a workflow for classifying mobile element insertions while elucidating their in-depth properties such as 5' truncations, internal inversion as well as source sites in the case of LINE1 transductions. Finally, we identify complex SVs probably caused by replication mechanisms or telomere crisis by examining the co-occurrence of multiple somatic SVs in common supporting reads. In summary, our approaches applied to cancer long-read sequencing data can reveal various features of somatic SVs and will lead to further understanding of mutational processes and functional consequences of somatic SVs.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.22.215699v1?rss=1

Authors: Rocher, V., Genais, M., Nassereddine, E., Mourad, R.

Abstract:

DNA is a complex molecule carrying the instructions an organism needs to develop, live and reproduce. In 1953, Watson and Crick discovered that DNA is composed of two chains forming a double-helix. Later on, other structures of DNA were discovered and shown to play important roles in the cell, in particular G-quadruplex (G4). Following genome sequencing, several bioinformatic algorithms were developed to map G4s in vitro based on a canonical sequence motif, G-richness and G-skewness or alternatively sequence features including k-mers, and more recently deep learning. Here, we propose a novel convolutional neural network (DeepG4) to map active G4s (forming both in vitro and in vivo). DeepG4 is very accurate to predict active G4s, while most state-of-the-art algorithms fail. Moreover, DeepG4 identifies key DNA motifs that are predictive of G4 activity. We found that active G4 motifs do not follow a very flexible sequence pattern as current algorithms seek for. Instead, active G4s are determined by numerous specific motifs. Moreover, among those motifs, we identified known transcription factors which could play important roles in G4 activity by contributing either directly to G4 structures themselves or indirectly by participating in G4 formation in the vicinity. Lastly, variant analysis suggests that SNPs altering predicted G4 activity could affect transcription and chromatin, e.g. gene expression, H3K4me3 mark and DNA methylation. Thus, DeepG4 paves the way for future studies assessing the impact of known disease-associated variants on DNA secondary structure by providing a mechanistic interpretation of SNP impact on transcription and chromatin.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.23.215525v1?rss=1

Authors: Cortal, A. L., Martignetti, L., Six, E., Rausell, A.

Abstract:

The exhaustive exploration of human cell heterogeneity requires the unbiased identification of molecular signatures that can serve as unique cell identity cards for every cell in the body. However, the stochasticity associated with high-throughput single-cell RNA sequencing has made it necessary to use clustering-based computational approaches in which the transcriptional characterization of cell-type heterogeneity is performed at cell-subpopulation level rather than at full single-cell resolution. We present here Cell-ID, a clustering-free multivariate statistical method for the robust extraction of per-cell gene signatures from single-cell RNA-seq. Cell-ID allows unbiased cell identity recognition across different donors, tissues-of-origin, model organisms and single-cell omics protocols. Cell-ID is distributed as an open-source R software package: https://github.com/RausellLab/CelliD.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.22.215459v1?rss=1

Authors: Janssens, R., Zhang, X., Kauffmann, A., de Weck, A., Durand, E. Y.

Abstract:

The identification and discovery of phenotypes from high content screening (HCS) images is a challenging task. Earlier works use image analysis pipelines to extract biological features, supervised training methods or generate features with neural networks pretrained on non-cellular images. We introduce a novel fully unsupervised deep learning algorithm to cluster cellular images with similar Mode-of-Action together using only the images pixel intensity values as input. The method outperforms existing approaches on the labelled subset of the BBBC021 dataset and achieves an accuracy of 97.09% for correctly classifying the Mode-of-Action (MOA) by nearest neighbors matching. One unique aspect of the approach is that it is able to perform training on the entire unannotated dataset, to correctly cluster similar treatments beyond the annotated subset of the dataset and can be used for novel MOA discovery.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.23.217364v1?rss=1

Authors: Kirzhner, V., Toledano-Kitai, D., Volkovich, Z.

Abstract:

Determination of metagenome composition is still one of the most interesting problems of bioinformatics. It involves a wide range of mathematical methods, from probabilistic models of combinatorics to cluster analysis and pattern recognition techniques. The successful advance of rapid sequencing methods and fast and precise metagenome analysis will increase the diagnostic value of healthy or pathological human metagenomes. The article presents the theoretical foundations of the algorithm for calculating the number of different genomes in the medium under study. The approach is based on analysis of the compositional spectra of subsequently sequenced samples of the medium. Its essential feature is using random fluctuations in the bacteria number in different samples of the same metagenome. The possibility of effective implementation of the algorithm in the presence of data errors is also discussed. In the work, the algorithm of a metagenome evaluation is described, including the estimation of the genome number and the identification of the genomes with known compositional spectra. It should be emphasized that evaluating the genome number in a metagenome can be always helpful, regardless of the metagenome separation techniques, such as clustering the sequencing results or marker analysis.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.22.215558v1?rss=1

Authors: Smedley, N., Aberle, D. R., Hsu, W.

Abstract:

PurposeTo investigate the use of deep neural networks to learn associations between gene expression and radiomics or histology in non-small cell lung cancer (NSCLC).

Materials and MethodsDeep feedforward neural networks were used for radio-genomic mapping, where 21,766 gene expressions were inputs to individually predict histology and 101 CT radiomic features. Models were compared against logistic regression, support vector machines, random forests, and gradient boosted trees on 262 training and 89 testing patients. Neural networks were interpreted using gene masking to derive the learned associations between subsets of gene expressions to a radiomic feature or histology type.

ResultsNeural networks outperformed other classifiers except in five radiomic features, where training differences were <0.026 AUC. In testing, neural networks classified histology with AUCs of 0.86 (adenocarcinoma), 0.91 (squamous), and 0.71 (other); and 14 radiomics features with >= 0.70 AUC. Gene masking of the models showed new and previously reported histology-gene or radiogenomic associations. For example, hypoxia genes could predict histology with >0.90 test AUC and published gene signatures for histology prediction were also predictive in our models (>0.80 test AUC). Gene sets related to the immune or cardiac systems and cell development processes were predictive (>0.70 test AUC) of several different radiomic features while AKT signaling, TNF, and Rho gene sets were each predictive of tumor textures.

ConclusionWe demonstrate the ability of neural networks to map gene expressions to radiomic features and histology in NSCLC and interpret the models to identify predictive genes associated with each feature or type.

Author SummaryNon-small-cell lung cancer (NSCLC) patients can have different presentations as seen in the CT scans, tumor gene expressions, or histology types. To improve the understanding of these complementary data types, this study attempts to map tumor gene expressions associated with a patients CT radiomic features or a histology type. We explore a deep neural network approach to learn gene-radiomic associations (i.e., the subsets of co-expressed genes that are predictive of a value of an individual radiomic feature) and gene-histology associations in two separate public cohorts. Our modeling approach is capable of learning relevant information by showing the model can predict histology and that the learned relationships are consistent with prior works. The study provides evidence for coherent patterns between gene expressions and radiomic features and suggests such integrated associations could improve patient stratification.

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