PaperPlayer biorxiv genomics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.09.243378v1?rss=1

Authors: Williams, A. M., Itgen, M. W., Broz, A. K., Carter, O. G., Sloan, D. B.

Abstract:

The angiosperm genus Silene is a model system for several traits of ecological and evolutionary significance in plants, including breeding system and sex chromosome evolution, host-pathogen interactions, invasive species biology, heavy metal tolerance, and cytonuclear interactions. Despite its importance, genomic resources for this large genus of approximately 850 species are scarce, with only one published whole-genome sequence (from the dioecious species S. latifolia). Here, we provide genomic and transcriptomic resources for a hermaphroditic representative of this genus (S. noctiflora), including a PacBio Iso-Seq transcriptome, which uses long-read, single-molecule sequencing technology to analyze full-length mRNA transcripts and identify paralogous genes and alternatively spliced genes. Using these data, we have assembled and annotated high-quality full-length cDNA sequences for approximately 17,000 S. noctiflora genes and 27,000 isoforms. We demonstrated the utility of these data to distinguish between recent and highly similar gene duplicates by identifying novel paralogous genes in an essential protease complex. Further, we provide a draft assembly for the approximately 2.7-Gb genome of this species, which is near the upper range of genome-size values reported for diploids in this genus and three-fold larger than the 0.9-Gb genome of S. conica, another species in the same subgenus. Karyotyping confirmed that S. noctiflora is a diploid, indicating that its large genome size is not due to polyploidization. These resources should facilitate further study and development of this genus as a model in plant ecology and evolution.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.10.243949v1?rss=1

Authors: Marla, S. S., Mishra, P., Maurya, R., Singh, M., Wankhade, D. P., Gupta, A. K., N, S. R., Singh, S. K., Kumar, R.

Abstract:

Recent developments in genome sequencing of several important crops helped to enrich our understanding of basic biology and immensely contributed to crop improvement. However, assembly of short reads from large plant genomes remains a challenge in computational biology despite major developments in Next Generation sequencing. Of late multiple draft assemblies are reported for a single genome of an organism result in availability of data with different levels of genome completeness. Reported draft assemblies of Cajanus cajan often are shorter than the referenced original genome as portions of genome missing. Gene coverage i.e. number of sequenced raw reads mapped on to certain locations of the genome is an important quality parameter in assembly process. Genomes with high map accuracy are essential for prediction of desired genes for crop researchers.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.10.244814v1?rss=1

Authors: Breuss, M. W., Yang, X., Antaki, D., Schlachetzki, J. C. M., Lana, A. A., Xu, X., Chai, G., Stanley, V., Song, Q., Fang Newmeyer, T., Nguyen, A., Cao, B., Nott, A., McEvoy-Venneri, J., Pasillas, M. P., Nahas, S., Van Der Kraan, L., Ding, Y., NIMH Brain Somatic Mosaicism Network,, Glass, C. K., Gleeson, J. G.

Abstract:

The structure of the human neocortex underlies species-specific features and is a reflection of intricate developmental programs. Here we analyzed neocortical cellular lineages through a comprehensive assessment of brain somatic mosaicism - which acts as a neutral recorder of lineage history. We employed deep whole genome and variant sequencing in a single postmortem neurotypical human brain across 25 anatomic regions and three distinct modalities: bulk geographies, sorted cell types, and single nuclei. We identified 259 mosaic variants, revealing remarkable differences in localization, clonal abundance, cell type specificity, and clade distribution. We identified a set of hierarchical cellular diffusion barriers, whereby the left-right axis separation of the neocortex occurs prior to anterior-posterior and dorsal-ventral axis separation. We also found that stochastic distribution is a driver of clonal dispersion, and that rules regarding cellular lineages and anatomical boundaries are often ignored. Our data provides a comprehensive analysis of brain somatic mosaicism across the human cerebral cortex, deconvolving clonal distributions and migration patterns in the human embryo.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.10.242677v1?rss=1

Authors: Bhoyar, R. C., Jain, A., Sehgal, P., Divakar, M. K., Sharma, D., Imran, M., Jolly, B., Ranjan, G., Rophina, M., Sharma, S., Siwach, S., Pandhare, K., Sahoo, S., Sahoo, M., Nayak, A., Mohanty, J. N., Das, J., Bhandari, S., Mathur, S. K., Kumar, A., Sahlot, R., Rojarani, P., Vijaya Lakshmi, J., Surekha, A., Sekhar, P. C., Mahajan, S., Masih, S., Singh, P., Kumar, V., Jose, B., Mahajan, V., Gupta, V., Gupta, R., Arumugam, P., Singh, A., Nandy, A., P.V., R., Jha, R. M., Kumari, A., Gandotra, S., Rao, V., Faruq, M., Kumar, S., Reshma G, B., Varma, N. G., Shekhar Roy, S., Sengupta, A., Chattopadhyay

Abstract:

The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance and for determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2. We used the approach on 752 clinical samples in duplicates, amounting to a total of 1536 samples which could be sequenced on a single S4 sequencing flow cell on NovaSeq 6000. Our analysis suggests a high concordance between technical duplicates and a high concordance of detection of SARS-CoV-2 between the COVIDSeq as well as RT-PCR approaches. An in-depth analysis revealed a total of six samples in which COVIDSeq detected SARS-CoV-2 in high confidence which were negative in RT-PCR. Additionally, the assay could detect SARS-CoV-2 in 21 samples and 16 samples which were classified inconclusive and pan-sarbeco positive respectively suggesting that COVIDSeq could be used as a confirmatory test. The sequencing approach also enabled insights into the evolution and genetic epidemiology of the SARS-CoV-2 samples. The samples were classified into a total of 3 clades. This study reports two lineages B.1.112 and B.1.99 for the first time in India. This study also revealed 1,143 unique single nucleotide variants and added a total of 73 novel variants identified for the first time. To the best of our knowledge, this is the first report of the COVIDSeq approach for detection and genetic epidemiology of SARS-CoV-2. Our analysis suggests that COVIDSeq could be a potential high sensitivity assay for the detection of SARS-CoV-2, with an additional advantage of enabling genetic epidemiology of SARS-CoV-2.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.10.241430v1?rss=1

Authors: Bortolini, E., Pagani, L., Oxilia, G., Posth, C., Fontana, F., Badino, F., Saupe, T., Montinaro, F., Margaritora, D., Romandini, M., Lugli, F., Papini, A., Boggioni, M., Perrini, N., Oxilia, A., Aiese Cigliano, R., Barcelona, R., Visentin, D., Fasser, N., Arrighi, S., Figus, C., Marciani, G., Silvestrini, S., Bernardini, F., Menghi Sartorio, J. C., Fiorenza, L., Moggi Cecchi, J., Tuniz, C., Kivisild, T., Gianfrancesco, F., Peresani, M., Scheib, C. L., Talamo, S., D'Esposito, M., Benazzi, S.

Abstract:

The end of the Last Glacial Maximum (LGM) in Europe (~16.5 ka ago) set in motion major changes in human culture and population structure. In Southern Europe, Early Epigravettian material culture was replaced by Late Epigravettian art and technology about 18-17 ka ago at the beginning of southern Alpine deglaciation, although available genetic evidence from individuals who lived ~14 ka ago opened up questions on the impact of migrations on this cultural transition only after that date. Here we generate new genomic data from a human mandible uncovered at the Late Epigravettian site of Riparo Tagliente (Veneto, Italy), that we directly dated to 16,980-16,510 cal BP (2{sigma}). This individual, affected by a low-prevalence dental pathology named focal osseous dysplasia, attests that the very emergence of Late Epigravettian material culture in Italy was already associated with migration and genetic replacement of the Gravettian-related ancestry. In doing so, we push back by at least 3,000 years the date of the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bolling/Allerod warming event (~14 ka ago). Our results suggest that demic diffusion from a genetically diverse population may have substantially contributed to cultural changes in LGM and post-LGM Southern Europe, independently from abrupt shifts to warmer and more favourable conditions.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.06.236307v1?rss=1

Authors: Giehr, P., Kyriakopoulos, C., Karl Nordström, K., Salhab, A., Müller, F., von Meyenn, F., Ficz, G., Reik, W., Wolf, V., Walter, J.

Abstract:

Background: DNA methylation is an essential epigenetic modification which is set and maintained by DNA methyl transferases (Dnmts) and removed via active and passive mechanisms involving Tet mediated oxidation. While the molecular mechanisms of these enzymes are well studied, their interplay on shaping cell specific methylomes remains less well understood. In our work we model the activities of Tets and Dnmts at single CpGs across the genome using a novel type of high resolution sequencing data. Results: To accurately measure 5mC and 5hmC levels at single CpGs we developed RRHPoxBS, a reduced representation hairpin oxidative bisulfite sequencing approach. Using this method we mapped the methylomes and hydroxymethylomes of wild type and Tet triple knockout mouse embryonic stem cells. These comprehensive datasets were then used to develop an extended Hidden Markov model allowing us i) to determine the symmetrical methylation and hydroxymethylation state at millions of individual CpGs, ii) infer the maintenance and de novo methylation efficiencies of Dnmts and the hydroxylation efficiencies of Tets at individual CpG positions. We find that Tets exhibit their highest activity around unmethylated regulatory elements, i.e., active promoters and enhancers. Furthermore, we find that Tets' presence has a profound effect on the global and local maintenance and de novo methylation activities by the Dnmts, not only substantially contributing to a universal demethylation of the genome but also shaping the overall methylation landscape. Conclusions: Our analysis demonstrates that a fine tuned and locally controlled interplay between Tets and Dnmts is important to modulate de novo and maintenance activities of Dnmts across the genome. Tet activities contribute to DNA methylation patterning in the following ways: They oxidize 5mC, they locally shield DNA from accidental de novo methylation and at the same time modulate maintenance and de novo methylation activities across the genome.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.06.240564v1?rss=1

Authors: Ben-David, E., Pliota, P., Widen, S. A., Koreshova, A., Lemus-Vergara, T., Verpukhovskiy, P., Mandali, S., Braendle, C., Burga, A., Kruglyak, L.

Abstract:

Toxin-antidote elements (TAs) are selfish genetic dyads that spread in populations by selectively killing non-carriers. TAs are common in prokaryotes, but few examples are known in animals. We discovered five maternal-effect TAs in the nematode Caenorhabditis tropicalis and one in C. briggsae. Unlike previously reported TAs, five of these novel toxins do not kill embryos but instead cause larval arrest or developmental delay. We identified the genes underlying a TA causing developmental delay, slow-1/grow-1, and found that the toxin, slow-1, is homologous to nuclear hormone receptors. Last, we found that balancing selection of conflicting TAs hampers their ability to drive in populations, leading to more stable genetic incompatibilities. Our results show that TAs are common in Caenorhabditis species, target a wide range of developmental processes, and may act as barriers preventing gene flow.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.07.241695v1?rss=1

Authors: Peck, L., Barraclough, T., Nowell, R., Flood, J., Ryan, M.

Abstract:

Nearly 50% of crop yields are lost to pests and disease, with plants and pathogens locked in an amplified co-evolutionary process of disease outbreaks. Coffee wilt disease, caused by Fusarium xylarioides, decimated coffee production in west and central Africa following an initial 1920s outbreak. After successful management, it later re-emerged reaching two separate epidemics by the 2000s on arabica coffee in Ethiopia and robusta coffee in east and central Africa. Here, we use genome sequencing of six historical culture collection strains spanning 70 years to identify the evolutionary processes behind these repeated outbreaks. The robusta population arose from the initial outbreak, whilst the arabica population is divergent and emerged independently. The two populations evolved similar pathologies by separately acquiring different effector genes horizontally via transposable elements from other Fusarium taxa, including F. oxysporum. Thus, historical genomics can help reveal mechanisms that allow fungal pathogens to keep pace with humanity's efforts to resist them.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.07.240069v1?rss=1

Authors: Liu, S., Wu, I., Yu, Y.-P., Balamotis, M., Ren, B.-G., Yehezkel, T. B., Luo, J.-H.

Abstract:

Diversity in human gene expression stems, to a large extent, from splicing exons into multiple mRNA isoforms. Characterization of isoforms requires accurate long-read sequencing. However, read lengths, high error rates, low throughput and large input requirements are some of the challenges that remain to be addressed in sequencing technologies. In this study, we used a barcoding-based synthetic long read (SLR) isoform sequencing approach, LoopSeq, to generate sequencing reads sufficiently long and accurate to identify isoforms using standard short read Illumina sequencers. The method identifies isoforms from control RNA samples with 99.4% accuracy and a 0.01% per-base error rate, exceeding the accuracy reported for other long-read sequencing technologies. Applied to targeted transcriptome sequencing of over 10,000 genes from colon cancers and their metastatic counterparts, LoopSeq revealed large scale isoform redistributions from benign colon mucosa to primary colon cancer and metastatic cancer and identified several novel gene fusion isoforms in the colon cancer samples. Strikingly, our data showed that most single nucleotide variants (SNVs) occurred dominantly in specific isoforms and that some SNVs underwent isoform switching in cancer progression.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.08.07.241828v1?rss=1

Authors: Noack, F., Vangelisti, S., Carido, M., Chong, F., Bonev, B.

Abstract:

Despite huge advances in stem-cell, single-cell and epigenetic technologies, the precise molecular mechanisms that determine lineage specification remain largely unknown. Applying an integrative multiomics approach, e.g. combining single-cell RNA-seq, single-cell ATAC-seq together with cell-type-specific DNA methylation and 3D genome measurements, we systematically map the regulatory landscape in the mouse neocortex in vivo. Our analysis identifies thousands of novel enhancer-gene pairs associated with dynamic changes in chromatin accessibility and gene expression along the differentiation trajectory. Crucially, we provide evidence that epigenetic remodeling generally precedes transcriptional activation, yet true priming appears limited to a subset of lineage-determining enhancers. Notably, we reveal considerable heterogeneity in both contact strength and dynamics of the generally cell-type-specific enhancer-promoter contacts. Finally, our work suggests a so far unrecognized function of several key transcription factors which act as putative "molecular bridges" and facilitate the dynamic reorganization of the chromatin landscape accompanying lineage specification in the brain.

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