GTex: Alles vernetzt Groß, Michael
Chemie in unserer Zeit,
12/2017, Letnik:
51, Številka:
6
Journal Article
Recenzirano
Das Netzwerk eines lebenden Organismus ist unglaublich kompliziert, wie wir in dieser Serie an ausgewählten Beispielen gesehen haben. Das menschliche Genom ist nur einer der Ansatzpunkte zur ...Erschließung der Zusammenhänge. Um medizinisch relevante Einblicke in die Ursachen von Krankheiten zu gewinnen, müssen wir verstehen lernen, wie das im ganzen Körper nahezu einheitliche Genom in verschiedenen Zellen und Geweben zu völlig verschiedenen Ausprägungen (Phänotypen) führt, und wie diese Verbindungen durch Mutationen beeinflusst werden. Diese gigantische Aufgabe geht das Gtex‐Projekt (Genotype Tissue Expression) an, das soeben eine umfassende Auswertung seiner Ergebnisse publiziert hat.
Three carbapenem-resistant
Escherichia coli
were recovered from rectal swabs of different patients in a tertiary hospital and were found carrying
bla
NDM-4,
an uncommon
bla
NDM
variant. Genome ...sequences of the isolates were obtained using Illumina technology and the long-read MinION sequencer. The isolates belonged to ST405 and phylogenetic group D, a globally distributed lineage associated with antimicrobial resistance. In addition to
bla
NDM-4
, the three isolates carried 14 known resistance genes including the extended-spectrum β-lactamase gene
bla
CTX-M-15
. There were only 1 or 2 SNPs between the isolates, suggesting a common origin and cryptic transmission in hospital.
bla
NDM-4
was located on a 46.5-kb IncFIA self-transmissible plasmid, which may facilitate further dissemination of
bla
NDM-4
. Two copies of IS
26
bracketed a 14.6-kb region containing
bla
NDM-4
and have the potential to form a composite transposon for mediating the mobilization of
bla
NDM-4
.
Throughout the animal kingdom, mitochondria are the only organelles that retain their own genome and the transcription and translation machineries that are all essential for energy harvesting. ...Mitochondria have developed a complex communication network, allowing them to stay in tune with cellular needs and nuclear transcriptional programs and to alleviate mitochondrial dysfunction. Here, we review recent findings on the wide array of mechanisms that contribute to these mitocellular communication networks, spanning from well-studied messenger molecules to mitonuclear genetic interactions. Based on these observations and developments, we advocate a broad and inclusive view on mitocellular interactions, which can have profound impacts on physiological, pathological, and evolutionary processes.
Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are ...thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.
The recent successes of the Materials Genome Initiative have opened up new opportunities for data-centric informatics approaches in several subfields of materials research, including in polymer ...science and engineering. Polymers, being inexpensive and possessing a broad range of tunable properties, are widespread in many technological applications. The vast chemical and morphological complexity of polymers though gives rise to challenges in the rational discovery of new materials for specific applications. The nascent field of polymer informatics seeks to provide tools and pathways for accelerated property prediction (and materials design) via surrogate machine learning models built on reliable past data. We have carefully accumulated a data set of organic polymers whose properties were obtained either computationally (bandgap, dielectric constant, refractive index, and atomization energy) or experimentally (glass transition temperature, solubility parameter, and density). A fingerprinting scheme that captures atomistic to morphological structural features was developed to numerically represent the polymers. Machine learning models were then trained by mapping the fingerprints (or features) to properties. Once developed, these models can rapidly predict properties of new polymers (within the same chemical class as the parent data set) and can also provide uncertainties underlying the predictions. Since different properties depend on different length-scale features, the prediction models were built on an optimized set of features for each individual property. Furthermore, these models are incorporated in a user-friendly online platform named Polymer Genome (www.polymergenome.org). Systematic and progressive expansion of both chemical and property spaces are planned to extend the applicability of Polymer Genome to a wide range of technological domains.
Monascus purpureus
, a pigment-producing ascomycetous fungus, has been traditionally used for red rice preparation using solid-state fermentation. The objective of this study was to develop an ...improved pigment-producing strain of
M. purpureus
MTCC 1090 through genome shuffling followed by detailed analytical estimations of pigments and other bioactive compounds produced by the fusant. Protoplast formation was optimum with 12 h-old mycelia incubated at 30 °C with cellulase, lyticase, and chitinase (40:1:1) for 5 h. Four UV-induced mutants that produced 13.1–39.5% higher amount of yellow, orange, and red pigments in fermented low-grade (cheap) broken rice were used as parents for genome shuffling. After the first round of fusion, four fusants with 35.9–60.52% higher pigment production capabilities were fused again, and finally the fusant F2-19 with distinct culture characteristic was selected under multi-selection pressure. It consistently produced 67%, 70%, and 76% higher content of yellow, orange, and red pigments respectively as compared to the wild-type. High-performance liquid chromatography (HPLC) analysis also reveals clear variation in pigment productions between wild-type and the fusant. Furthermore, HPLC analysis of F2-19 fermented rice extract confirms the production of 186 ± 8.71 and 3810 ± 29.81 mg/kg mevinolin and gamma-aminobutyric acid respectively. Citrinin was not detected. F2-19 fermented rice also has high antioxidant activity (7.92 ± 0.32 mg/g trolox equivalent), with good amount of phenolics (18.0 ± 0.95 mg/g gallic acid equivalent) and flavonoids (2.7 ± 0.26 mg/g quercetin equivalent). Thus, genome shuffling was successfully implemented on
M. purpureus
for the first time to develop a citrinin-free, better-performing fusant that holds future biotechnological potential.
Key points
• Genome shuffling was performed by recursive protoplast fusion in Monascus purpureus.
• The selected fusant, F2-19, was used in solid-state fermentation using low-grade rice.
• It produced 67–76% higher content of yellow, orange, and red pigments than the wild-type.
• HPLC detected 186 mg/kg mevinolin and 3810 mg/kg γ-aminobutyric acid, but no citrinin.
• F2-19 shows high antioxidant activity with good amount of phenolics and flavonoids.
Graphical abstract
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Lithium–sulfur (Li–S) batteries are considered as promising candidates for next-generation energy storage devices due to their ultrahigh theoretical gravimetric energy density, ...cost-effectiveness, and environmental friendliness. However, the application of Li–S batteries remains challenging, mainly due to a lack of understanding of the complex chemical reactions and associated equilibria occurring in a working Li–S system. In this review, the typical applications of computational chemistry in Li–S battery studies, correlating to characterization techniques, such as X-ray diffraction, infra-red & Raman spectra, X-ray absorption spectroscopy, binding energy, and nuclear magnetic resonance, are reviewed. In particular, high-accuracy calculations and large-scale models, materials genome, and machine-learning approaches are expected to further advance computational design for the development of Li–S batteries and related fields.
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The Materials Genome Initiative (MGI) has heralded a sea change in the philosophy of materials design. In an increasing number of applications, the successful deployment of novel ...materials has benefited from the use of computational methodologies, data descriptors, and machine learning. Polymers have long suffered from a lack of data on electronic, mechanical, and dielectric properties across large chemical spaces, causing a stagnation in the set of suitable candidates for various applications. Extensive efforts over the last few years have seen the fruitful application of MGI principles toward the accelerated discovery of attractive polymer dielectrics for capacitive energy storage. Here, we review these efforts, highlighting the importance of computational data generation and screening, targeted synthesis and characterization, polymer fingerprinting and machine-learning prediction models, and the creation of an online knowledgebase to guide ongoing and future polymer discovery and design. We lay special emphasis on the fingerprinting of polymers in terms of their genome or constituent atomic and molecular fragments, an idea that pays homage to the pioneers of the human genome project who identified the basic building blocks of the human DNA. By scoping the polymer genome, we present an essential roadmap for the design of polymer dielectrics, and provide future perspectives and directions for expansions to other polymer subclasses and properties.
High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for ...only a few non-microbial species
. To address this issue, the international Genome 10K (G10K) consortium
has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are ...consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.