PaperPlayer biorxiv genomics

Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.28.224386v1?rss=1

Authors: Das, J., Roy, S.

Abstract:

Prevailing pandemic across the world due to SARSCoV-2 drawing great attention towards discovering its evolutionary origin. We perform an exploratory study to understand the variability of the whole coding region of possible proximal evolutionary neighbours of SARSCoV-2. We consider seven (07) human coronavirus strains from six different species as a candidate for our study. First, we observe a good variability of nucleotides across candidate strains. We did not find a significant variation of GC content across the strains for codon position first and second. However, we interestingly see huge variability of GC-content in codon position 3rd (GC3), and pairwise mean GC-content (SARS-CoV, MERS-CoV), and (SARSCoV-2, hCoV229E) are quite closer. While observing the relative abundance of dinucleotide feature, we find a shared typical genetic pattern, i.e., high usage of GC and CT nucleotide pair at the first two positions (P12) of codons and the last two positions (P23) of codons, respectively. We also observe a low abundance of CG pair that might help in their evolution bio-process. Secondly, Considering RSCU score, we find a substantial similarity for mild class coronaviruses, i.e., hCoVOC43, hCoVHKU1, and hCoVNL63 based on their codon hit with high RSCU value ([≥] 1:5), and a minimum number of codons hit (count-9) is observed for MERS-CoV. We see seven codons ATT, ACT, TCT, CCT, GTT, GCT and GGT with high RSCU value, which are common in all seven strains. These codons are mostly from Aliphatic and Hydroxyl amino acid group. A phylogenetic tree built using RSCU feature reveals proximity among hCoVOC43 and hCoV229E (mild). Thirdly, we perform linear regression analysis among GC content in different codon position and ENC value. We observe a strong correlation (significant p-value) between GC2 and GC3 for SARSCoV-2, hCoV229E and hCoVNL63, and between GC1 and GC3 for hCoV229E, hCoVNL63, SARSCoV. We believe that our findings will help in understanding the mechanism of human coronavirus.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.27.222349v1?rss=1

Authors: Zheng, Y.-F., Chen, Z.-C., Shi, Z.-X., Hu, K.-H., Zhong, J.-Y., Wang, C.-X., Shi, W., Chen, Y., Xie, S.-Q., Luo, F., Bo, X., Tang, C., Liu, Y.-Z., Xiao, C.-L.

Abstract:

Single-cell isoform sequencing can reveal transcriptomic dynamics in individual cells invisible to bulk- and single-cell RNA analysis based on short-read sequencing. However, current long-read single-cell sequencing technologies have been limited by low throughput and high error rate. Here we introduce HIT-scISOseq for high-throughput single-cell isoform sequencing. This method was made possible by full-length cDNA capture using biotinylated PCR primers, and by our novel library preparation procedure that combines head-to-tail concatemeric full-length cDNAs into a long SMRTbell insert for high-accuracy PacBio sequencing. HIT-scISOseq yields > 10 million high-accuracy full-length isoforms in a single PacBio Sequel II 8M SMRT Cell, providing > 8 times more data output than the standard single-cell isoform PacBio sequencing protocol. We exemplified HIT-scISOseq by first studying transcriptome profiles of 4,000 normal and 8,000 injured corneal epitheliums from cynomolgus monkeys. We constructed dynamic transcriptome landscapes of known and rare cell types, revealed novel isoforms, and identified injury-related splicing and switching events that are previously not accessible with low throughput isoform sequencing. HIT-scISOseq represents a high-throughput, cost-effective, and technically simple method to accelerate the burgeoning field of long-read single-cell transcriptomics.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.27.218867v1?rss=1

Authors: Qu, L., Wang, L., He, F., Han, Y., Yang, L., Wang, M. D., Zhu, H.

Abstract:

Background: Variations in the human genome have been studied extensively. However, little is known about the role of micro-inversions (MIs), generally defined as small (<100 bp) inversions, in human evolution, diversity, and health. Depicting the pattern of MIs among diverse populations is critical for interpreting human evolutionary history and obtaining insight into genetic diseases. Results: In this paper, we explored the distribution of MIs in genomes from 26 human populations and 7 nonhuman primate genomes and analyzed the phylogenetic structure of the 26 human populations based on the MIs. We further investigated the functions of the MIs located within genes associated with human health. With hg19 as the reference genome, we detected 6,968 MIs among the 1,937 human samples and 24,476 MIs among the 7 nonhuman primate genomes. The analyses of MIs in human genomes showed that the MIs were rarely located in exonic regions. Nonhuman primates and human populations shared only 82 inverted alleles, and Africans had the most inverted alleles in common with nonhuman primates, which was consistent with the Out of Africa hypothesis. The clustering of MIs among the human populations also coincided with human migration history and ancestral lineages. Conclusions: We propose that MIs are potential evolutionary markers for investigating population dynamics. Our results revealed the diversity of MIs in human populations and showed that they are essential to constructing human population relationships and have a potential effect on human health.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.27.223172v1?rss=1

Authors: Picardi, E., Mansi, L., Pesole, G.

Abstract:

ADAR1-mediated deamination of adenosines in long double stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2 infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions and are, in the majority of cases, nonsynonymous. The impact of RNA editing on virus-host interactions could be relevant to identify potential targets for therapeutic interventions.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.27.223628v1?rss=1

Authors: Fox, K., Huerta-Sanchez, E., Villanea, F. A.

Abstract:

Variation at the ABO locus was one of the earliest sources of data in the study of human population identity and history, and to this day remains widely genotyped due to its importance in blood and tissue transfusions. As one of the first genetic markers, variation at the ABO gene has been studied for over 60 years, and yet there are some aspects of its evolution that remain mysterious. Here, we look at ABO blood type variants in our archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic landscape of the ABO gene in archaic humans, and how it relates to modern human ABO variation. We analyze coding variation at the ABO locus from next-generation sequences in ~2,500 individuals from 28 populations, including three Neanderthal and one Denisovan individuals. We use the modern human haplotypes to impute ABO genotypes for the four archaic human genomes. We found that the Siberian Neanderthals, Altai and Chagyrskaya, are both homozygous for a derived Neanderthal variant of the O allele, while the European Neanderthal, Vindija, is a heterozygote for two derived Neanderthal variants, an O variant different from Altai and Chagyrskaya, and a rare cis-AB variant. The Denisovan individual is homozygous for an ancestral variant of the O allele, similar to variants found widely in modern humans. Perhaps more surprisingly, the derived O allele variant found in the Altai Neanderthal can be found at low frequencies in modern European and Southeast Asian individuals, and the derived O allele variant found in the Vindija Neanderthal is also found at very low frequency in East Asian individuals. Our genetic distance analyses suggests both alleles were introgressed through Neanderthal-human gene flow. In summary, our study identifies the genetic variation of the ABO gene in archaic humans, we find that ABO allele diversity in Neanderthals was likely high, and that some of these alleles still survive in modern humans due to inbreeding with Neanderthals.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.24.218818v1?rss=1

Authors: Yamaguchi, K., Hara, Y., Kaori, T., Nishimura, O., Smith, J., Kadota, M., Kuraku, S.

Abstract:

The group of hagfishes (Myxiniformes) arose from agnathan (jawless vertebrate) lineages and is one of the only two extant cyclostome taxa, together with lampreys (Petromyzontiformes). Even though whole genome sequencing has been achieved for diverse vertebrate taxa, genome-wide sequence information has been highly limited for cyclostomes. Here we sequenced the genome of the inshore hagfish Eptatretus burgeri using DNA extracted from the testis, with a short-read sequencing platform, aiming at reconstructing a high-coverage coding gene catalogue. The obtained genome assembly, scaffolded with mate-pair reads and paired RNA-seq reads, exhibited an N50 scaffold length of 293 Kbp, which allowed the genome-wide prediction of coding genes. This computation resulted in the gene models whose completeness was estimated at the complete coverage of more than 83 % and the partial coverage of more than 93 % by referring to evolutionarily conserved single-copy orthologs. The high contiguity of the assembly and completeness of resulting gene models promises a high utility in various comparative analyses including phylogenomics and phylome exploration.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.25.199281v1?rss=1

Authors: Escoda, L., Castresana, J.

Abstract:

The Pyrenean desman (Galemys pyrenaicus) is a small semiaquatic mammal endemic to the Iberian Peninsula. Despite its limited range, this species presents a strong genetic structure due to past isolation in glacial refugia and subsequent bottlenecks. Additionally, some populations are highly fragmented today as a consequence of river barriers, causing substantial levels of inbreeding. These features make the Pyrenean desman a unique model in which to study the genomic footprints of differentiation, bottlenecks and extreme isolation in an endangered species. The complete genome of the Pyrenean desman was assembled using a Bloom filter-based approach. An analysis of the 1.83 Gb reference genome and the sequencing of five additional individuals from different evolutionary units allowed us to detect its main genomic characteristics. The population differentiation of the species was reflected in highly distinctive demographic trajectories. A severe population bottleneck during the postglacial recolonization of the eastern Pyrenees created the lowest genomic heterozygosity ever recorded in a mammal. Moreover, isolation and inbreeding gave rise to a high proportion of runs of homozygosity (ROH). Despite these extremely low levels of genetic diversity, two key multigene families from an eco-evolutionary perspective that need to be genetically variable, the major histocompatibility complex and olfactory receptor genes, showed heterozygosity excess in the majority of individuals. Furthermore, these two classes of genes were significantly less abundant than expected within ROH. These results allow us to characterize important genomic health indicators for each individual, information that may be crucial for the conservation and management of the species.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.26.220608v1?rss=1

Authors: Babarinde, I. A., Ma, G., Li, Y., Deng, B., Luo, Z., Liu, H., Abdul, M., Ward, C., Chen, M., Fu, X., Duttlinger, M., He, J., Sun, L., Li, W., Zhuang, Q., Frampton, J., Cazier, J.-B., Chen, J., Jauch, R., Esteban, M. A., Hutchins, A.

Abstract:

Transposable elements (TEs) occupy nearly 50% of mammalian genomes and are both potential dangers to genome stability and functional genetic elements. TEs can be expressed and exonised as part of a transcript, however, their full contribution to the transcript splicing remains unresolved. Here, guided by long and short read sequencing of RNAs, we show that 26% of coding and 65% of non-coding transcripts of human pluripotent stem cells (hPSCs) contain TEs. Different TE families have unique integration patterns with diverse consequences on RNA expression and function. We identify hPSC-specific splicing of endogenous retroviruses (ERVs) as well as LINE L1 elements into protein coding genes that generate TE-derived peptides. Finally, single cell RNA-seq reveals that proliferating hPSCs are dominated by ERV-containing transcripts, and subpopulations express SINE or LINE-containing transcripts. Overall, we demonstrate that TE splicing modulates the pluripotency transcriptome by enhancing and impairing transcript expression and generating novel transcripts and peptides.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.25.220673v1?rss=1

Authors: Pritykin, Y., van der Veeken, J., Pine, A., Zhong, Y., Sahin, M., Mazutis, L., Pe'er, D., Rudensky, A., Leslie, C. S.

Abstract:

CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across different experimental and clinical settings. By carrying out a unified analysis of over 300 ATAC-seq and RNA-seq experiments from twelve independent studies of CD8 T cell dysfunction in cancer and infection we defined a shared differentiation trajectory towards terminal dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell activation states across models. Experimental dissection of acute and chronic viral infection using scATAC-seq and allele-specific scRNA-seq identified state-specific transcription factors and captured the early emergence of highly similar TCF1+ progenitor-like populations at an early branch point, at which epigenetic features of functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.

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Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.24.212712v1?rss=1

Authors: Wagner, J., Olson, N. D., Harris, L., Khan, Z., Farek, J., Mahmoud, M., Stankovic, A., Kovacevic, V., Wenger, A. M., Rowell, W. J., Xiao, C., Yoo, B., Miller, N., Rosenfeld, J. A., Ni, B., Zarate, S., Kirsche, M., Aganezov, S., Schatz, M., Narzisi, G., Byrska-Bishop, M., Clarke, W., Evani, U. S., Markello, C., Shafin, K., Zhou, X., Sidow, A., Bansal, V., Martinez Barrio, A., Fiddes, I. T., Fungtammasan, A., Chin, C.-S., Sedlazeck, F. J., Carroll, A., Salit, M., Zook, J. M., Genome in a Bottle Consortium

Abstract:

Genome in a Bottle (GIAB) benchmarks have been widely used to validate clinical sequencing pipelines and develop new variant calling and sequencing methods. Here we use accurate long and linked reads to expand the prior benchmark to include difficult-to-map regions and segmental duplications that are not readily accessible to short reads. Our new benchmark adds more than 300,000 SNVs, 50,000 indels, and 16 % new exonic variants, many in challenging, clinically relevant genes not previously covered (e.g., PMS2). We increase coverage of the GRCh38 assembly from 85 % to 92 %, while excluding problematic regions for benchmarking small variants (e.g., copy number variants and assembly errors) that should not have been in the previous version. Our new benchmark reliably identifies both false positives and false negatives across multiple short-, linked-, and long-read based variant calling methods. As an example of its utility, this benchmark identifies eight times more false negatives in a short read variant call set relative to our previous benchmark, mostly in difficult-to-map regions. To enable robust small variant benchmarking, we still exclude 3.6% of GRCh37 and 5.0% of GRCh38 in (1) highly repetitive regions such as large, highly similar segmental duplications and the centromere not accessible to our data and (2) regions where our sample is highly divergent from the reference due to large indels, structural variation, copy number variation, and/or errors in the reference (e.g., some KIR genes that have duplications in HG002). We have demonstrated the utility of this benchmark to assess performance in more challenging regions, which enables benchmarking in more difficult genes and continued technology and bioinformatics development. The benchmarks are available at: ftp://ftp-trace.ncbi.nlm.nih.gov/ReferenceSamples/giab/release/AshkenazimTrio/HG002_NA24385_son/NISTv4.1/ ftp://ftp-trace.ncbi.nlm.nih.gov/ReferenceSamples/giab/data/AshkenazimTrio/analysis/NIST_v4.2_SmallVariantDraftBenchmark_07092020/

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