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Combinatorial genomics

C De La Fuente Canto, D I Kalogiros, M Ptashnyk, T S George, R Waugh, A G Bengough, J Russell, L X Dupuy
Discoveries on the genetics of resource acquisition efficiency are limited by the ability to measure plant roots in sufficient number and adequate genotypic variability. This paper presents a root phenotyping study that explores ways to combine live imaging and computer algorithms for model-based extraction of root growth parameters. The study is based on a subset of barley Recombinant Chromosome Substitution Lines (RCSLs) and a combinatorial approach was designed for fast identification of the regions of the genome that contribute the most to variations in root system architecture (RSA)...
March 17, 2018: Journal of Theoretical Biology
Ye Jianwen, Hu Dingkai, Che Xuemei, Jiang Xiaoran, Li Teng, Chen Jinchun, Zhang Haoqian, Chen Guo-Qiang
Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] is one of the most promising biomaterials expected to be used in a wide range of scenarios. However, its large-scale production is still hindered by the high cost. Here we report the engineering of Halomonas bluephagenesis as a low-cost platform for non-sterile and continuous fermentative production of P(3HB-co-4HB) from glucose. Two interrelated 4-hydroxybutyrate (4HB) biosynthesis pathways were constructed to guarantee 4HB monomer supply for P(3HB-co-4HB) synthesis by working in concert with 3-hydroxybutyrate (3HB) pathway...
March 15, 2018: Metabolic Engineering
Yamin Li, Tao Yang, Yingjie Yu, Nicola Shi, Liu Yang, Zachary Glass, Justin Bolinger, Isaac James Finkel, Wenhan Li, Qiaobing Xu
Protein based therapeutics with high specificities and low off-target effects are used for transient and accurate manipulation of cell functions. However, developing safe and efficient carriers for intracellular delivery of active therapeutic proteins is a long-standing challenge. Here we report a combinatorial library of chalcogen (O, S, Se) containing lipidoid nanoparticles (LNPs) as efficient nanocarriers for intracellular delivery of negatively supercharged Cre recombinase ((-30)GFP-Cre) and anionic Cas9:single-guide RNA (Cas9:sgRNA) ribonucleoprotein (RNP) for genome editing...
March 8, 2018: Biomaterials
Wei Wang, Claudia Racioppi, Basile Gravez, Lionel Christiaen
Genome-wide studies in Ciona often require highly purified cell populations. In this methods chapter, we introduce multi-channel combinatorial fluorescence activated cells sorting (FACS) and magnetic-activated cell sorting (MACS) as two sensitive and efficient tools for isolating lineage-specific cell populations from dissociated Ciona embryos and larvae. We present isolation of trunk ventral cell (TVC) progeny as the test case most commonly used in our laboratory. These approaches may also be applied to purify other cell populations with the proper combination of tissue-specific reporters...
2018: Advances in Experimental Medicine and Biology
Darren A Cusanovich, James P Reddington, David A Garfield, Riza M Daza, Delasa Aghamirzaie, Raquel Marco-Ferreres, Hannah A Pliner, Lena Christiansen, Xiaojie Qiu, Frank J Steemers, Cole Trapnell, Jay Shendure, Eileen E M Furlong
Understanding how gene regulatory networks control the progressive restriction of cell fates is a long-standing challenge. Recent advances in measuring gene expression in single cells are providing new insights into lineage commitment. However, the regulatory events underlying these changes remain unclear. Here we investigate the dynamics of chromatin regulatory landscapes during embryogenesis at single-cell resolution. Using single-cell combinatorial indexing assay for transposase accessible chromatin with sequencing (sci-ATAC-seq), we profiled chromatin accessibility in over 20,000 single nuclei from fixed Drosophila melanogaster embryos spanning three landmark embryonic stages: 2-4 h after egg laying (predominantly stage 5 blastoderm nuclei), when each embryo comprises around 6,000 multipotent cells; 6-8 h after egg laying (predominantly stage 10-11), to capture a midpoint in embryonic development when major lineages in the mesoderm and ectoderm are specified; and 10-12 h after egg laying (predominantly stage 13), when each of the embryo's more than 20,000 cells are undergoing terminal differentiation...
March 14, 2018: Nature
Xiang-Tian Yu, Tao Zeng
The diversity and huge omics data take biology and biomedicine research and application into a big data era, just like that popular in human society a decade ago. They are opening a new challenge from horizontal data ensemble (e.g., the similar types of data collected from different labs or companies) to vertical data ensemble (e.g., the different types of data collected for a group of person with match information), which requires the integrative analysis in biology and biomedicine and also asks for emergent development of data integration to address the great changes from previous population-guided to newly individual-guided investigations...
2018: Methods in Molecular Biology
Alessandro Vannozzi, Darren Chern Jan Wong, Janine Höll, Ibrahim Hmmam, José Tomás Matus, Jochen Bogs, Tobias Ziegler, Ian Dry, Gianni Barcaccia, Margherita Lucchin
Stilbene synthase (STS) is the key enzyme leading to the biosynthesis of resveratrol. Recently we reported two R2R3-MYB transcription factors (TFs) that regulate the stilbene biosynthetic pathway in grapevine: VviMYB14 and VviMYB15. These genes strongly co-express with STSs under a range of stress and developmental conditions, in agreement with the specific activation of STS promoters by these TFs. Genome-wide gene co-expression analysis using two separate transcriptome compendia based on microarray and RNA-Seq data revealed that WRKY TFs were the top TF family correlated with STS genes...
February 26, 2018: Plant & Cell Physiology
Albertas Dvirnas, Christoffer Pichler, Callum L Stewart, Saair Quaderi, Lena K Nyberg, Vilhelm Müller, Santosh Kumar Bikkarolla, Erik Kristiansson, Linus Sandegren, Fredrik Westerlund, Tobias Ambjörnsson
The output from whole genome sequencing is a set of contigs, i.e. short non-overlapping DNA sequences (sizes 1-100 kilobasepairs). Piecing the contigs together is an especially difficult task for previously unsequenced DNA, and may not be feasible due to factors such as the lack of sufficient coverage or larger repetitive regions which generate gaps in the final sequence. Here we propose a new method for scaffolding such contigs. The proposed method uses densely labeled optical DNA barcodes from competitive binding experiments as scaffolds...
2018: PloS One
Jill L Silverman, Jacob Ellegood
PURPOSE OF REVIEW: This review highlights the invaluable contribution of in-vivo rodent models in dissecting the underlying neurobiology for numerous neurodevelopmental disorders. Currently, models are routinely generated with precision genomics and characterized for research on neurodevelopmental disorders. In order to impact translation, outcome measures that are translationally relevant are essential. This review emphasizes the importance of accurate neurobehavioral and anatomical analyses...
April 2018: Current Opinion in Neurology
Philipp E Merkl, Megan Orzalli, David M Knipe
The initial events after DNA virus infection involve a race between epigenetic silencing of the incoming viral DNA by host cell factors and expression of viral genes. Several host gene products, including the nuclear domain 10 (ND10) components PML (promyelocytic leukemia) and Daxx (death domain-associated protein 6), as well as IFI16 (interferon-inducible protein 16), have been shown to restrict herpes simplex virus 1 (HSV-1) replication. Whether IFI16 and ND10 components work together or separately to restrict HSV-1 replication is not known...
February 28, 2018: Journal of Virology
K Makay White, Melinda K Matthews, Rachel Hughes, Andrew J Sommer, Joel S Griffitts, Peter D Newell, John M Chaston
A metagenome wide association (MGWA) study of bacterial host association determinants in Drosophila predicted that LPS biosynthesis genes are significantly associated with host colonization. We were unable to create site-directed mutants for each of the predicted genes in Acetobacter , so we created an arrayed transposon insertion library using Acetobacter fabarum DsW_054 isolated from Drosophila Creation of the A. fabarum DsW_054 gene knock-out library was performed by combinatorial mapping and Illumina sequencing of random transposon insertion mutants...
February 27, 2018: G3: Genes—Genomes—Genetics
Ibrahim Numanagić, Salem Malikić, Michael Ford, Xiang Qin, Lorraine Toji, Milan Radovich, Todd C Skaar, Victoria M Pratt, Bonnie Berger, Steve Scherer, S Cenk Sahinalp
High-throughput sequencing provides the means to determine the allelic decomposition for any gene of interest-the number of copies and the exact sequence content of each copy of a gene. Although many clinically and functionally important genes are highly polymorphic and have undergone structural alterations, no high-throughput sequencing data analysis tool has yet been designed to effectively solve the full allelic decomposition problem. Here we introduce a combinatorial optimization framework that successfully resolves this challenging problem, including for genes with structural alterations...
February 26, 2018: Nature Communications
Liye He, Jing Tang, Emma I Andersson, Sanna Timonen, Steffen Koschmieder, Krister Wennerberg, Satu Mustjoki, Tero Aittokallio
The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway crosstalk, personalized combination treatments targeting multiple cancer growth and survival pathways are required. Here we implemented a computational-experimental drug combination prediction and testing (DCPT) platform for efficient in silico prioritization and ex vivo testing in patient-derived samples to identify customized synergistic combinations for individual cancer patients...
February 26, 2018: Cancer Research
Richard H Baltz
The original article can be found online at .
February 26, 2018: Journal of Industrial Microbiology & Biotechnology
Binghui Liu, Chong Wu, Xiaotong Shen, Wei Pan
Next-generation sequencing studies on cancer somatic mutations have discovered that driver mutations tend to appear in most tumor samples, but they barely overlap in any single tumor sample, presumably because a single driver mutation can perturb the whole pathway. Based on the corresponding new concepts of coverage and mutual exclusivity, new methods can be designed for de novo discovery of mutated driver pathways in cancer. Since the computational problem is a combinatorial optimization with an objective function involving a discontinuous indicator function in high dimension, many existing optimization algorithms, such as a brute force enumeration, gradient descent and Newton's methods, are practically infeasible or directly inapplicable...
September 2017: Annals of Applied Statistics
Rongming Liu, Liya Liang, Andrew D Garst, Alaksh Choudhury, Violeta Sànchez I Nogué, Gregg T Beckham, Ryan T Gill
Strain engineering for industrial production requires a targeted improvement of multiple complex traits, which range from pathway flux to tolerance to mixed sugar utilization. Here, we report the use of an iterative CRISPR EnAbled Trackable genome Engineering (iCREATE) method to engineer rapid glucose and xylose co-consumption and tolerance to hydrolysate inhibitors in E. coli. Deep mutagenesis libraries were rationally designed, constructed, and screened to target ~40,000 mutations across 30 genes. These libraries included global and high-level regulators that regulate global gene expression, transcription factors that play important roles in genome-level transcription, enzymes that function in the sugar transport system, NAD(P)H metabolism, and the aldehyde reduction system...
February 22, 2018: Metabolic Engineering
Min-Sun Jin, Hyebin Lee, Jongmin Woo, Seongmin Choi, Mi Sol Do, Kwangsoo Kim, Min Ji Song, Youngsoo Kim, In Ae Park, Dohyun Han, Han Suk Ryu
PURPOSE: Secretory carcinoma (SC) of the breast is defined as an indolent tumor but is still categorized into a basal-like triple-negative breast cancer (BL-TNBC) subgroup that generally shows aggressive behaviour according to the current classification. Despite the unique clinical behaviour of SC, molecular characteristics that reflect biological behaviours of SC remain largely unknown. EXPERIMENTAL DESIGN: We employed a combinatorial approach of whole-exome sequencing and mass spectrometry-based in-depth quantitative proteomics to determine the entire molecular landscape of SC using three SC formalin-fixed paraffin-embedded (FFPE) tissues...
February 24, 2018: Proteomics. Clinical Applications
Verena Thormann, Maika C Rothkegel, Robert Schöpflin, Laura V Glaser, Petar Djuric, Na Li, Ho-Ryun Chung, Kevin Schwahn, Martin Vingron, Sebastiaan H Meijsing
No abstract text is available yet for this article.
February 19, 2018: Nucleic Acids Research
Miao He, Z Josh Huang
Understanding brain circuit organization and function requires systematic dissection of its cellular components. With vast cell number and diversity, mammalian nervous systems present a daunting challenge for achieving specific and comprehensive cell type access-prerequisite to circuit analysis. Genetic approaches in the mouse have relied on germline engineering to access marker-defined cell populations. Combinatorial strategies that engage marker intersection, anatomy and projection pattern (e.g. antero-grade and retro-grade viral vectors), and developmental lineage substantially increase the specificity of cell type targeting...
February 19, 2018: Current Opinion in Neurobiology
Zheng Hu, Zhaoying Shi, Xiaogang Guo, Baishan Jiang, Guo Wang, Dixian Luo, Yonglong Chen, Yuan-Shan Zhu
Background: Precise genome editing is essential for both basic and translational research. The recently developed CRISPR/Cas9 system can specifically cleave a designated site of target gene to create a DNA double-strand break, which triggers cellular DNA repair mechanism of either inaccurate non-homologous end joining, or site-specific homologous recombination. Unfortunately, homology-directed repair (HDR) is challenging due to its very low efficiency. Herein, we focused on improving the efficiency of HDR using a combination of CRISPR/Cas9, eGFP, DNA ligase IV inhibitor SCR7, and single-stranded oligodeoxynucleotides (ssODN) in human cancer cells...
2018: Cell & Bioscience
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