PaperPlayer biorxiv genomics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.07.238329v1?rss=1

Authors: Oleksyk, T. K., Wolfsberger, W. W., Weber, A., Shchubelka, K., Oleksyk, O. T., Levchuk, O., Patrus, A., Lazar, N., Castro-Marquez, S. O., Boldyzhar, P., Urbanovych, A., Stakhovska, V., Malyar, K., Chervyakova, S., Podoroha, O., Kovalchuk, N., Hasynets, Y., Rodriguez-Flores, J. L., Medley, S., Battistuzzi, F. U., Liu, R., Hou, Y., Chen, S., Yang, H., Yeager, M., Dean, M., Mills, R. E., Smolanka, V.

Abstract:

The main goal of this collaborative effort is to provide genome wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for the public data release. DNBSEQ-G50 sequences, and genotypes by an Illumina GWAS chip were cross-validated on multiple samples, and additionally referenced to a sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. The genome data has been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, CNVs, SNPs and microsatellites. This study is providing the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for historic and medical research in a large understudied population. While most of the common variation is shared with other European populations, this survey of population variation contributes a number of novel SNPs and structural variants that have not been reported in the gnomAD/1KG databases representing global distribution of genomic variation. These endemic variants will become a valuable resource for designing future population and clinical studies, help address questions about ancestry and admixture, and will fill a missing place in the puzzle characterizing human population diversity in Eastern Europe. Our results indicate that genetic diversity of the Ukrainian population is uniquely shaped by the evolutionary and demographic forces, and cannot be ignored in the future genetic and biomedical studies. This data will contribute a wealth of new information bringing forth different risk and/or protective alleles. The newly discovered low frequency and local variants can be added to the current genotyping arrays for genome wide association studies, clinical trials, and in genome assessment of proliferating cancer cells.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.07.240911v1?rss=1

Authors: Steidele, C. E., Stam, R.

Abstract:

The receptor-like protein (RLP) family is a complex gene family with 57 members in Arabidopsis thaliana. Some members of the RLP family are known to be involved in basal developmental processes, whereas others have found to be involved in defence responses. However, functional data is to date, only available for a small subset of RLPs, leaving the remaining ones classified as RLPs of unknown function. Using publicly available datasets, we annotated those RLPs of unknown functions as either likely defence-related or likely fulfilling a more basal function in plants. Using these categories, we can identify important characteristics that differ between the RLP sub classes. We find the two classes differ in abundance on both transcriptome and proteome level, physical clustering in the genome and putative interaction partners. However, the classes do not differ in the genetic diversity of their individual members in accessible pan-genome data. Our work has several implications for work related to functional studies on RLPs as well as for the understanding of RLP gene family evolution. Using our annotations, we can make suggestions of which RLPs can be identified as potential immune receptors using genetics tools, which can be useful for disease studies. The lack of differences in nucleotide diversity between the two RLP subclasses further suggests that non-synonymous diversity of gene sequences alone cannot distinguish defence from developmental genes. By contrast, differences in transcript and protein abundance or clustering at genomic loci might also allow for functional annotations and characterisation in other plant species.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.06.240754v1?rss=1

Authors: Ward, C. M., Ludington, A. J., Breen, J., Baxter, S. W.

Abstract:

The analysis and interpretation of datasets generated through sequencing large numbers of individual genomes is becoming commonplace in population and evolutionary genetic studies. Here we introduce geaR, a modular R package for evolutionary analysis of genome-wide genotype data. The package leverages the Genomic Data Structure (GDS) format, which enables memory and time efficient querying of genotype datasets compared to standard VCF genotype files. geaR utilizes GRange object classes to partition an analysis based on features from GFF annotation files, select codons based on position or degeneracy, and construct both positional and coordinate genomic windows. Tests of genetic diversity (eg. dXY, {pi}, FST) and admixture (f4, fd) along with tree building and sequence output, can be carried out on partitions using a single function regardless of sample ploidy or number of observed alleles. The package and associated documentation are available on GitHub at https://github.com/CMWbio/geaR.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.06.236117v1?rss=1

Authors: Cornick, J. E., Musicha, P., Peno, C., Saeger, E., Iroh-Tam, P.-Y., Bennett, A., Kennedy, N., Feasey, N., Heniz, E., Cain, A. K.

Abstract:

A suspected outbreak of multi-drug resistant (MDR) Klebsiella pneumoniae in a Malawian neonatal unit was investigated using whole-genome sequencing. Strain-types, virulence and resistance genes of K. pneumoniae isolated from patients in the hospital over a four-year period were identified. A MDR ST340 clone was implicated as the likely outbreak cause.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.04.234245v1?rss=1

Authors: Zou, X., Koh, G. C. C., Nanda, A. S., Degasperi, A., Urgo, K., Roumeliotis, T., Agu, C. A., Side, L., Brice, G., Perez-Alonso, V., Rueda, D., Badja, C., Young, J., Gomez, C., Bushell, W., Harris, R., Choudhary, J., Jiricny, J. I., Skarnes, W. C., Nik-Zainal, S.

Abstract:

Mutational signatures are imprints of pathophysiological processes arising through tumorigenesis. Here, we generate isogenic CRISPR-Cas9 knockouts ({Delta}) of 43 genes in human induced pluripotent stem cells, culture them in the absence of added DNA damage, and perform whole-genome sequencing of 173 daughter subclones. {Delta}OGG1, {Delta}UNG, {Delta}EXO1, {Delta}RNF168, {Delta}MLH1, {Delta}MSH2, {Delta}MSH6, {Delta}PMS1, and {Delta}PMS2 produce marked mutational signatures indicative of being critical mitigators of endogenous DNA changes. Detailed analyses reveal that 8-oxo-dG removal by different repair proteins is sequence-context-specific while uracil clearance is sequence-context-independent. Signatures of mismatch repair (MMR) deficiency show components of C>A transversions due to oxidative damage, T>C and C>T transitions due to differential misincorporation by replicative polymerases, and T>A transversions for which we propose a 'reverse template slippage' model. {Delta}MLH1, {Delta}MSH6, and {Delta}MSH2 signatures are similar to each other but distinct from {Delta}PMS2. We validate these gene-specificities in cells from patients with Constitutive Mismatch Repair Deficiency Syndrome. Based on these experimental insights, we develop a classifier, MMRDetect, for improved clinical detection of MMR-deficient tumors.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.05.237834v1?rss=1

Authors: Wang, Z., Wang, J., Kourakos, M., Hoang, N., Lee, H. H., Mathieson, I., Mathieson, S.

Abstract:

Population genetics relies heavily on simulated data for validation, inference, and intuition. In particular, since real data is always limited, simulated data is crucial for training machine learning methods. Simulation software can accurately model evolutionary processes, but requires many hand-selected input parameters. As a result, simulated data often fails to mirror the properties of real genetic data, which limits the scope of methods that rely on it. In this work, we develop a novel approach to estimating parameters in population genetic models that automatically adapts to data from any population. Our method is based on a generative adversarial network that gradually learns to generate realistic synthetic data. We demonstrate that our method is able to recover input parameters in a simulated isolation-with-migration model. We then apply our method to human data from the 1000 Genomes Project, and show that we can accurately recapitulate the features of real data.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.05.239004v1?rss=1

Authors: Jackson, E. W., Wilhelm, R. C., Johnson, M. R., Lutz, H. L., Danforth, I., Gaydos, J. K., Hart, M. H., Hewson, I. H.

Abstract:

A viral etiology of Sea Star Wasting Syndrome (SSWS) has been largely explored using metagenomics leading to the conclusion that a densovirus is the predominant DNA virus associated with this syndrome, and, thus, the most promising viral candidate pathogen. Single-stranded DNA viruses are however highly diverse and pervasive among eukaryotic organisms which we hypothesize may confound the association between densoviruses and SSWS in sea stars. To test this hypothesis and assess the association of densoviruses to SSWS, we compiled past metagenomic data with new metagenomic-derived viral genomes from sea stars collected from Antarctica, California, Washington, and Alaska. We used 179 publicly available sea star transcriptomes to complement our approaches for densovirus discovery. Lastly, we focus the study to SSaDV, the first sea star densovirus discovered, by documenting its biogeography and putative tissue tropism. Transcriptomes contained mostly endogenized densovirus elements similar to the NS1 gene, while >30 complete and near-complete densoviral genomes were recovered from viral metagenomes. SSaDV was associated with nearly all tested species from southern California to Alaska, and in contrast to previous work, we show SSaDV is one genotype among a high diversity of densoviruses present in sea stars across the west coast of the United States and globally that are commonly associated with grossly normal (i.e. healthy or asymptomatic) animals. The diversity and ubiquity of these viruses in wild sea stars confounds the original hypothesis that one densovirus was the etiologic agent of SSWD.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.06.240630v1?rss=1

Authors: Bell, R., Wolf, Y. I., Koonin, E. V.

Abstract:

Background: DNA and RNA of most cellular life forms and many viruses contain an expansive repertoire of modified bases. The modified bases play diverse biological roles that include both regulation of transcription and translation, and protection against restriction endonucleases and antibiotics. Modified bases are often recognized by dedicated protein domains. However, the elaborate networks of interactions and processes mediated by modified bases are far from being completely understood. Results: We present a comprehensive census and classification of EVE domains that belong to the PUA/ASCH domain superfamily and bind various modified bases in DNA and RNA. Prokaryotes encode two classes of EVE domain proteins, slow-evolving and fast-evolving. The slow-evolving EVE domains in alpha-proteobacteria are embedded in a conserved operonic context that implies involvement in coupling between translation and respiration, in particular, cytochrome c biogenesis, potentially, via binding 5-methylcytosine in tRNAs. In beta and gamma-proteobacteria, the conserved associations implicate the EVE domains in the coordination of cell division, biofilm formation, and global transcriptional regulation by non-coding 6S small RNAs, which are potentially modified and bound by the EVE domains. Down-regulation of the EVE-encoding operons might cause dormancy or programmed cell death (PCD). In eukaryotes, the EVE-domain-containing THYN1-like proteins appear to inhibit PCD and regulate the cell cycle, likely, via binding 5-methylcytosine and its derivatives in DNA and/or RNA. Thus, the link between PCD and cytochrome c that appears to be universal in eukaryotes might have been inherited from the -proteobacterial, proto-mitochondrial endosymbiont and, unexpectedly, could involve modified base recognition by EVE domains. In numerous prokaryotic genomes, fast-evolving EVE domains are embedded in defense contexts, including toxin-antitoxin modules and Type IV restriction systems, all of which can also induce PCD. These EVE domains likely recognize modified bases in invading DNA molecules and target them for restriction. We additionally identified EVE-like prokaryotic Development and Cell Death (DCD) domains that are also implicated in defense functions including PCD. This function was inherited by eukaryotes but, in animals, the DCD proteins apparently were displaced by the extended Tudor family, whose partnership with Piwi-related Argonautes became the centerpiece of the piRNA system. Conclusions: Recognition of modified bases in DNA and RNA by EVE-like domains appears to be an important, but until now, under-appreciated, common denominator in a variety of processes including PCD, cell cycle control, antivirus immunity, stress response and germline development in animals.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.06.239277v1?rss=1

Authors: Zhang, W., Xie, C., Ullrich, K. K., Zhang, Y. E., Tautz, D.

Abstract:

Gene retroposition is known to contribute to patterns of gene evolution and adaptations. However, possible negative effects of gene retroposition remain largely unexplored, since most previous studies have focussed on between-species comparisons where negatively selected copies are mostly not observed, as they are quickly lost from the populations. Here, we show for natural house mouse populations that the primary rate of retroposition is orders of magnitude higher than previously thought. Comparisons with SNP distribution patterns in the same populations show that most retroposition events are deleterious. Transcriptomic profiling analysis shows that new retroposed copies become easily subject to transcription and have an influence on the expression level of their parental genes, especially when transcribed in the antisense direction. Our results imply that the impact of retroposition on the mutational load in natural populations has been highly underestimated, which has also major implications for strategies of disease allele detection in humans.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.05.238972v1?rss=1

Authors: Henderson, A. N., Govindarajulu, R., Hawkins, J. S.

Abstract:

Soil salinity impedes crop production via both osmotic and ionic stress and is an intensifying problem affecting lands used to produce agronomically important crops.. Such stress slows plant growth and disrupts normal metabolic processes, resulting in decreased biomass and increased leaf senescence. Therefore, the ability to maintain biomass in response to salt exposure is indicative of tolerant genotypes. We used a recombinant inbred line (RIL) population derived from an interspecific cross between Sorghum propinquum and Sorghum bicolor (inbred Tx7000), two genotypes that differ for tolerance to salt exposure, to map regions of the genome associated with salt tolerance. Our high-density genetic map covers the 10 Sorghum chromosomes with 1692 segregating markers. Sixteen total quantitative trait loci (QTL) were detected for seven traits in two environmental conditions (control and salt) and when stress tolerance index (STI) values were mapped. Our results uncovered significant enrichment of genes encoding various types of aquaporins within salt specific QTL, the most interesting of which is the plasma-membrane intrinsic protein SbPIP2;6. SbPIP2;6 shares ~85% sequence similarity with Arabidopsis PIP2;1, an aquaporin shown to co-transport both water and ions, and for which ion transport is inhibited by calcium, suggesting that it may play a role in sensing and signaling during the salt stress response. The coupling of water and ion transport may also facilitate the use of Na+ as a cheap compatible solute, reducing the energy needed to maintain osmotic equilibrium. These results indicate that PIPs play a central role in salinity tolerance in sorghum.

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