scholarly journals Nematode Functional Genomics

Yeast ◽  
2000 ◽  
Vol 1 (1) ◽  
pp. 43-47
Keyword(s):  
Functional Genomics ◽  
Human Genome ◽  
Genome Sequence ◽  
Protein Interactions ◽  
Dna Microarrays ◽  
Molecular Mechanisms ◽  
Physical Map ◽  
Cell Signalling ◽  
Genome Project ◽  
C Elegans

Alan Coulson has two main roles at the Sanger Centre, revolving around the worm and the human genome projects. Although the worm sequence is essentially finished, the tidying-up of that and the physical map is ongoing. There is also a continuous need for communication with the worm field with regard to information and materials relating to the sequence project. For example, the cosmids and YACs of the physical map continue to be, as they have been for many years now, an extremely powerful resource, and the Sanger Centre distributes in the order of 500 clones per month to the community.Alan is team leader of the worm functional genomics group, which is currently small but will be expanding shortly. Patricia Kuwabara is a member of the team and a description of their activities can be found below. The Human Genome Project is sequencing mapped PAC and BAC clones. Alan's primary involvement is with the team that is responsible for subcloning the 10 000 or so clones that will be required to complete the one-third of the genome sequence to be contributed by the Sanger Centre.Patricia Kuwabara has been using Caenorhabditis elegans as a model for understanding how protein–protein interactions regulate cell-to-cell signalling. Her research has focused on understanding the molecular mechanisms underlying the genetics of C. elegans sex determination. This work has led into a study of regulated proteolysis involving calpains and also into the roles of the multiple C. elegans Patched proteins, which in other organisms have been shown to be receptors for the Hedgehog morphogen.In addition, the group is taking advantage of the completion of the C. elegans genome sequence to develop whole genome DNA microarrays for expression profiling. At the Sanger Centre, DNA microarrays are providing opportunities to examine how development and physiology are regulated globally, because most nematode genes have now been identified at the sequence level. The group are being assisted in this endeavour by Dr Stuart Kim (Stanford, CA).

scholarly journals Recent advances in functional genome analysis

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1968 ◽  
Author(s):  
Roderic Guigo ◽  
Michiel de Hoon
Keyword(s):  
Functional Genomics ◽  
Human Genome ◽  
Large Scale ◽  
Massively Parallel Sequencing ◽  
Genome Project ◽  
Biological Traits ◽  
Cellular Behavior ◽  
Sequencing Technologies ◽  
Recent Advances ◽  
The Human Genome Project

At the beginning of this century, the Human Genome Project produced the first drafts of the human genome sequence. Following this, large-scale functional genomics studies were initiated to understand the molecular basis underlying the translation of the instructions encoded in the genome into the biological traits of organisms. Instrumental in the ensuing revolution in functional genomics were the rapid advances in massively parallel sequencing technologies as well as the development of a wide diversity of protocols that make use of these technologies to understand cellular behavior at the molecular level. Here, we review recent advances in functional genomic methods, discuss some of their current capabilities and limitations, and briefly sketch future directions within the field.

scholarly journals I’ll Show You Mine, If You Show Me Yours

2001 ◽  
Vol 1 ◽  
pp. 33-33
Keyword(s):  
Human Genome ◽  
Genome Sequence ◽  
Human Genome Project ◽  
Genome Project ◽  
Human Genome Sequence ◽  
Publicly Funded ◽  
Private Company ◽  
Science News

The human genome dominated science news last week. Both Science and Nature lead this week with articles about the simultaneous publication of the human genome sequence by the private company Celera Genomics and the publicly funded Human Genome Project (HGP).

scholarly journals Bcl-2 Family Proteins in Development and Treatment of Malignant Diseases

2011 ◽  
Vol 11 (3) ◽  
pp. 15-23 ◽  
Author(s):  
P. Racay ◽  
J. Jurecekova ◽  
A. Stefanikova ◽  
K. Klikova ◽  
J. Hatok ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Cell Signalling ◽  
Acquired Resistance ◽  
Therapy Response ◽  
Mitochondrial Pathway ◽  
New Drugs ◽  
Malignant Cells ◽  
Malignant Diseases

Bcl-2 Family Proteins in Development and Treatment of Malignant DiseasesProteins of Bcl-2 family are key regulators of mitochondrial pathway of apoptosis. Deregulation of apoptosis disrupts the complex and delicate balance between cell proliferation, survival and death and plays an important role in the development of malignant diseases. In addition to uncontrolled proliferation, alterations in apoptotic proteins are frequently associated with resistance of malignant cells to chemotherapy, leading to ineffective treatment with chemotherapy that primarily acts by apoptosis initiation. Despite the progress in combinatory and biologic therapy, response rates for treatment of different malignant diseases are not high enough. Therefore, new anti-cancer agents that selectively kill tumour cells and spare normal tissues are still urgently needed. Progress in biochemistry and cell biology leading to detailed dissection of cell signalling pathways allows development of new therapeutic strategies targeting different proteins involved in malignant transformation and uncontrolled proliferation of malignant cells. Emerging knowledge on molecular mechanisms of apoptosis deregulation in cancer development has revealed Bcl-2 family proteins as potential targets for drugs discovery. Structural analysis of these proteins together with studies of apoptosis mechanisms have outlined strategies for generation of new drugs, resulting in numerous novel chemical entities with mechanism-based activity. Many of the most logical targets for promoting apoptosis of malignant cells are technically challenging, involving often disruption of protein interactions or changes in gene expression, as opposed to traditional pharmaceutical approach that predominantly attacks enzymes. Understanding of the core components of the apoptotic machinery at the molecular and structural levels may lead to new era in cancer therapy where the intrinsic and acquired resistance of malignant cells to apoptosis can be pharmacologically reversed, reinstating natural pathways of cell suicide.

scholarly journals Implementing solid-phase-enhanced sample preparation for Co-Immunoprecipitation with Mass Spectrometry for C. elegans

2021 ◽  
Author(s):  
Guelkiz Baytek ◽  
Oliver Popp ◽  
Philipp Mertins ◽  
Baris Tursun
Keyword(s):  
Mass Spectrometry ◽  
Sample Preparation ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Preparation Method ◽  
Solid Phase ◽  
Protein Protein Interactions ◽  
Sample Preparation Method ◽  
C Elegans

Studying protein-protein interactions in vivo can reveal key molecular mechanisms of biological processes. Co-Immunoprecipitation followed by Mass Spectrometry (CoIP-MS) allows detection of protein-protein interactions in high-throughput. The nematode Caenorhabditis elegans (C. elegans) is a powerful genetic model organism for in vivo studies. Yet, its rigid cuticle and complex tissues require optimization for protein biochemistry applications to ensure robustness and reproducibility of experimental outcomes. Therefore, we optimized CoIP-MS application to C. elegans protein lysates by combining a native CoIP procedure with an efficient sample preparation method called single-pot, solid-phase-enhanced, sample preparation method (SP3). Our results based on the subunits of the conserved chromatin remodeler FACT demonstrate that our SP3-integrated CoIP-MS procedure for C. elegans samples is highly accurate and robust. Moreover, in a previous study (Baytek et al. 2021), we extended our technique to studying the chromodomain factor MRG-1 (MRG15 in human), which resulted in unprecedented findings.

Genomics in 2K10: Fulfilling the Promise of a Sequenced Human Genome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-16-SCI-16
Author(s):  
Eric D. Green
Keyword(s):  
Human Genome ◽  
Genome Sequence ◽  
Genetic Basis ◽  
Conflicts Of Interest ◽  
Sequence Data ◽  
Genetic Diseases ◽  
Genomic Medicine ◽  
Genome Project ◽  
Human Genome Sequence ◽  
Genomics Research

Abstract Abstract SCI-16 The Human Genome Project's completion of the human genome sequence in 2003 was a landmark scientific achievement of historic significance. It also signified a critical transition for the field of genomics, as the new foundation of genomic knowledge started to be used in powerful ways by researchers and clinicians to tackle increasingly complex problems in biomedicine. To exploit the opportunities provided by the human genome sequence and to ensure the productive growth of genomics as one of the most vital biomedical disciplines of the 21st century, the National Human Genome Research Institute (NHGRI) is pursuing a broad vision for genomics research beyond the Human Genome Project. This vision includes facilitating and supporting the highest-priority research areas that interconnect genomics to biology, to health, and to society.Current efforts in genomics research are focused on using genomic data, technologies, and insights to acquire a deeper understanding of biology and to uncover the genetic basis of human disease. Some of the most profound advances are being catalyzed by revolutionary new DNA sequencing technologies; these methods are already producing prodigious amounts of DNA sequence data, including from large numbers of individual patients. Such a capability, coupled with better associations between genetic diseases and specific regions of the human genome, are accelerating our understanding of the genetic basis for complex genetic disorders and for drug response. Together, these developments will usher in the era of genomic medicine. Disclosures: No relevant conflicts of interest to declare.

DNA Microarrays

2009 ◽  
pp. 278-293 ◽  
Author(s):  
Aristotelis Chatziioannou ◽  
Panagiotis Moulos
Keyword(s):  
Statistical Analysis ◽  
Human Genome ◽  
High Throughput ◽  
Human Genome Project ◽  
Dna Microarrays ◽  
Technological Development ◽  
Genome Project ◽  
Biological Processes ◽  
Microarray Image ◽  
The Human Genome Project

The completion of the Human Genome Project and the emergence of high-throughput technologies at the dawn of the new millennium, are rapidly changing the way we approach biological problems. DNA microarrays represent a promising new technological development, widely used for the investigation and identification of genes associated with important biological processes. The chapter is divided in two parts: the first discusses current methods for the acquisition and quantitation of the microarray image while the second focuses in the analysis and interpretation of the microarray signals (standardization, normalization, statistical analysis etc.)

scholarly journals Assessment of community efforts to advance computational prediction of protein-protein interactions

2021 ◽  
Author(s):  
Xu-Wen Wang ◽  
Lorenzo Madeddu ◽  
Kerstin Spirohn ◽  
Leonardo Martini ◽  
Adriano Fazzone ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Computational Prediction ◽  
Superior Performance ◽  
Systematic Evaluation ◽  
Human Interactome ◽  
C Elegans ◽  
Protein Protein Interaction ◽  
Human Ppis ◽  
Underlying Network

AbstractComprehensive insights from the human protein-protein interaction (PPI) network, known as the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain unmapped. Computational approaches, especially network-based methods, can facilitate the identification of new PPIs. Many such approaches have been proposed. However, a systematic evaluation of existing network-based methods in predicting PPIs is still lacking. Here, we report community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 24 representative network-based methods to predict PPIs across five different interactomes, including a synthetic interactome generated by the duplication-mutation-complementation model, and the interactomes of four different organisms: A. thaliana, C. elegans, S. cerevisiae, and H. sapiens. We selected the top-seven methods through a computational validation on the human interactome. We next experimentally validated their top-500 predicted PPIs (in total 3,276 predicted PPIs) using the yeast two-hybrid assay, finding 1,177 new human PPIs (involving 633 proteins). Our results indicate that task-tailored similarity-based methods, which leverage the underlying network characteristics of PPIs, show superior performance over other general link prediction methods. Through experimental validation, we confirmed that the top-ranking methods show promising performance externally. For example, from the top 500 PPIs predicted by an advanced similarity-base method [MPS(B&T)], 430 were successfully tested by Y2H with 376 testing positive, yielding a precision of 87.4%. These results establish advanced similarity-based methods as powerful tools for the prediction of human PPIs.

scholarly journals Computational Tools forBrassica–ArabidopsisComparative Genomics

2005 ◽  
Vol 6 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Paul Beckett ◽  
Ian Bancroft ◽  
Martin Trick
Keyword(s):  
Genome Sequence ◽  
In Silico ◽  
Physical Map ◽  
Genome Structure ◽  
Genome Project ◽  
Genome Survey ◽  
Physical Maps ◽  
Alignment Tool ◽  
Wide Range ◽  
Survey Sequence

Recent advances, such as the availability of extensive genome survey sequence (GSS) data and draft physical maps, are radically transforming the means by which we can dissectBrassicagenome structure and systematically relate it to theArabidopsismodel. Hitherto, our view of the co-linearities between these closely related genomes had been largely inferred from comparative RFLP data, necessitating substantial interpolation and expert interpretation. Sequencing of theBrassica rapagenome by the MultinationalBrassicaGenome Project will, however, enable an entirely computational approach to this problem. Meanwhile we have been developing databases and bioinformatics tools to support our work inBrassicacomparative genomics, including a recently completed draft physical map ofB. rapaintegrated with anchor probes derived from theArabidopsisgenome sequence. We are also exploring new ways to display the emergingBrassica–Arabidopsissequence homology data. We have mapped all publicly available Brassica sequencesin silicoto theArabidopsisTIGR v5 genome sequence and published this in the ATIDB database that uses Generic Genome Browser (GBrowse). Thisin silicoapproach potentially identifies all paralogous sequences and so we colour-code the significance of the mappings and offer an integrated, real-time multiple alignment tool to partition them into paralogous groups. The MySQL database driving GBrowse can also be directly interrogated, using the powerful API offered by the Perl Bio∷DB∷GFF methods, facilitating a wide range of data-mining possibilities.

DNA Microarrays for Polymorphism Detection and Genotyping: Utility in the Understanding of Complex Neuropsychiatric Diseases

CNS Spectrums ◽  
1999 ◽  
Vol 4 (5) ◽  
pp. 59-74 ◽  
Author(s):  
Pamela Sklar ◽  
David Altshuler ◽  
Michele Cargill ◽  
Joel N. Hirschhorn
Keyword(s):  
Human Genome ◽  
Dna Microarrays ◽  
Comprehensive Evaluation ◽  
Genetic Diseases ◽  
Genome Project ◽  
Specific Gene ◽  
Dna And Rna ◽  
Neuropsychiatric Diseases ◽  
The Human Genome Project ◽  
Complex Genetic Diseases

AbstractAs the Human Genome Project completes the first human genome sequence, attention has turned to how this information can be used to understand disease. The availability of sequences for all genes will allow a comprehensive evaluation of each gene's contribution to disease. Approaches involving collecting specific gene variants and monitoring expression levels using DNA microarrays facilitate collecting information about DNA and RNA in a rapid and highly parallel manner. Developing an extensive catalogue of polymorphisms will become increasingly important in the context of studies of complex genetic diseases such as schizophrenia and bipolar disorder.

scholarly journals ntEdit: scalable genome assembly polishing

2019 ◽  
Author(s):  
René L Warren ◽  
Lauren Coombe ◽  
Hamid Mohamadi ◽  
Jessica Zhang ◽  
Barry Jaquish ◽  
...  
Keyword(s):  
Human Genome ◽  
Genome Sequence ◽  
Sequence Data ◽  
Bloom Filter ◽  
Routine Practice ◽  
High Coverage ◽  
E Coli ◽  
C Elegans ◽  
Illumina Sequence ◽  
Genome Assemblies

AbstractIn the modern genomics era, genome sequence assemblies are routine practice. However, depending on the methodology, resulting drafts may contain considerable base errors. Although utilities exist for genome base polishing, they work best with high read coverage and do not scale well. We developed ntEdit, a Bloom filter-based genome sequence editing utility that scales to large mammalian and conifer genomes.We first tested ntEdit and the state-of-the-art assembly improvement tools GATK, Pilon and Racon on controlled E. coli and C. elegans sequence data. Generally, ntEdit performs well at low sequence depths (<20X), fixing the majority (>97%) of base substitutions and indels, and its performance is largely constant with increased coverage. In all experiments conducted using a single CPU, the ntEdit pipeline executed in <14s and <3m, on average, on E. coli and C. elegans, respectively. We performed similar benchmarks on a sub-20X coverage human genome sequence dataset, inspecting accuracy and resource usage in editing chromosomes 1 and 21, and whole genome. ntEdit scaled linearly, executing in 30-40m on those sequences. We show how ntEdit ran in <2h20m to improve upon long and linked read human genome assemblies of NA12878, using high coverage (54X) Illumina sequence data from the same individual, fixing frame shifts in coding sequences. We also generated 17-fold coverage spruce sequence data from haploid sequence sources (seed megagametophyte), and used it to edit our pseudo haploid assemblies of the 20 Gbp interior and white spruce genomes in <4 and <5h, respectively, making roughly 50M edits at a (substitution+indel) rate of 0.0024.Availabilityhttps://github.com/bcgsc/nteditSupplemental materialavailable online.

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