Highlights d BALF cell transcriptome indicates robust innate immune responses in COVID-19 patients d COVID-19 patients exhibit chemokine-dominant hypercytokinemia d ISGs are highly expressed in COVID-19 patients and exhibit pathogenic potential

An elevated level of viral diversity was found in some SARS-CoV-2 infected patients, indicating the risk of rapid evolution of the virus. Although no evidence for the transmission of intra-host variants was found, the risk should not be overlooked. Abstract:Background A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung. MethodsWe have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls. ResultsThe median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences).However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked.The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.Conclusion SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa203/5780800 by guest on 16 March 2020 4 evolution in the population and associated clinical changes.

Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

Heteroplasmy, the existence of multiple mtDNA types within an individual, has been previously detected by using mostly indirect methods and focusing largely on just the hypervariable segments of the control region. Next-generation sequencing technologies should enable studies of heteroplasmy across the entire mtDNA genome at much higher resolution, because many independent reads are generated for each position. However, the higher error rate associated with these technologies must be taken into consideration to avoid false detection of heteroplasmy. We used simulations and phiX174 sequence data to design criteria for accurate detection of heteroplasmy with the Illumina Genome Analyzer platform, and we used artificial mixtures and replicate data to test and refine the criteria. We then applied these criteria to mtDNA sequence reads for 131 individuals from five Eurasian populations that had been generated via a parallel tagged approach. We identified 37 heteroplasmies at 10% frequency or higher at 34 sites in 32 individuals. The mutational spectrum does not differ between heteroplasmic mutations and polymorphisms in the same individuals, but the relative mutation rate at heteroplasmic mutations is significantly higher than that estimated for all mutable sites in the human mtDNA genome. Moreover, there is also a significant excess of nonsynonymous mutations observed among heteroplasmies, compared to polymorphism data from the same individuals. Both mutation-drift and negative selection influence the fate of heteroplasmies to determine the polymorphism spectrum in humans. With appropriate criteria for avoiding false positives due to sequencing errors, next-generation technologies can provide novel insights into genome-wide aspects of mtDNA heteroplasmy.

Heteroplasmy in human mtDNA may play a role in cancer, other diseases, and aging, but patterns of heteroplasmy variation across different tissues have not been thoroughly investigated. Here, we analyzed complete mtDNA genome sequences at ∼3,500× average coverage from each of 12 tissues obtained at autopsy from each of 152 individuals. We identified 4,577 heteroplasmies (with an alternative allele frequency of at least 0.5%) at 393 positions across the mtDNA genome. Surprisingly, different nucleotide positions (nps) exhibit high frequencies of heteroplasmy in different tissues, and, moreover, heteroplasmy is strongly dependent on the specific consensus allele at an np. All of these tissue-related and allele-related heteroplasmies show a significant age-related accumulation, suggesting positive selection for specific alleles at specific positions in specific tissues. We also find a highly significant excess of liver-specific heteroplasmies involving nonsynonymous changes, most of which are predicted to have an impact on protein function. This apparent positive selection for reduced mitochondrial function in the liver may reflect selection to decrease damaging byproducts of liver mitochondrial metabolism (i.e., "survival of the slowest"). Overall, our results provide compelling evidence for positive selection acting on some somatic mtDNA mutations.mtDNA | heteroplasmy | selection | human | tissue variation

Conductive hydrogels have emerged as promising material candidates for epidermal sensors due to their similarity to biological tissues, good wearability, and high accuracy of information acquisition. However, it is difficult to simultaneously achieve conductive hydrogel-based epidermal sensors with reliable healability for long-term usage, robust mechanical property, environmental degradability for decreased electronic waste, and sensing capability of the physiological stimuli and the electrophysiological signals. Herein, we propose the synthesis strategy of a multifunctional epidermal sensor based on the highly stretchable, self-healing, degradable, and biocompatible nanocomposite hydrogel, which is fabricated from the conformal coating of a MXene (Ti3C2T x ) network by the hydrogel polymer networks involving poly­(acrylic acid) and amorphous calcium carbonate. The epidermal sensor can be employed to sensitively detect human motions with the fast response time (20 ms) and to serve as electronic skins for wirelessly monitoring the electrophysiological signals (such as the electromyogram and electrocardiogram signals). Meanwhile, the multifunctional epidermal sensor could be degraded in phosphate buffered saline solution, which could not cause any pollution to the environment. This line of research work sheds light on the fabrication of the healable, degradable, and electrophysiological signal-sensitive conductive hydrogel-based epidermal sensors with potential applications in human–machine interactions, healthy diagnosis, and smart robot prosthesis devices.

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BackgroundAlthough the importance of the human oral microbiome for health and disease is increasingly recognized, variation in the composition of the oral microbiome across different climates and geographic regions is largely unexplored.ResultsHere we analyze the saliva microbiome from native Alaskans (76 individuals from 4 populations), Germans (10 individuals from 1 population), and Africans (66 individuals from 3 populations) based on next-generation sequencing of partial 16S rRNA gene sequences. After quality filtering, a total of 67,916 analyzed sequences resulted in 5,592 OTUs (defined at ≥97% identity) and 123 genera. The three human groups differed significantly by the degree of diversity between and within individuals (e.g. beta diversity: Africans > Alaskans > Germans; alpha diversity: Germans > Alaskans > Africans). UniFrac, network, ANOSIM, and correlation analyses all indicated more similarities in the saliva microbiome of native Alaskans and Germans than between either group and Africans. The native Alaskans and Germans also had the highest number of shared bacterial interactions. At the level of shared OTUs, only limited support for a core microbiome shared across all three continental regions was provided, although partial correlation analysis did highlight interactions involving several pairs of genera as conserved across all human groups. Subsampling strategies for compensating for the unequal number of individuals per group or unequal sequence reads confirmed the above observations.ConclusionOverall, this study illustrates the distinctiveness of the saliva microbiome of human groups living under very different climatic conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-014-0316-1) contains supplementary material, which is available to authorized users.