77 research outputs found
Meraculous: De Novo Genome Assembly with Short Paired-End Reads
We describe a new algorithm, meraculous, for whole genome assembly of deep paired-end short reads, and apply it to the assembly of a dataset of paired 75-bp Illumina reads derived from the 15.4 megabase genome of the haploid yeast Pichia stipitis. More than 95% of the genome is recovered, with no errors; half the assembled sequence is in contigs longer than 101 kilobases and in scaffolds longer than 269 kilobases. Incorporating fosmid ends recovers entire chromosomes. Meraculous relies on an efficient and conservative traversal of the subgraph of the k-mer (deBruijn) graph of oligonucleotides with unique high quality extensions in the dataset, avoiding an explicit error correction step as used in other short-read assemblers. A novel memory-efficient hashing scheme is introduced. The resulting contigs are ordered and oriented using paired reads separated by âŒ280 bp or âŒ3.2 kbp, and many gaps between contigs can be closed using paired-end placements. Practical issues with the dataset are described, and prospects for assembling larger genomes are discussed
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s}=1.96 TeV using Lepton + Jets Events with Secondary Vertex b-tagging
We present a measurement of the ttbar production cross section using events
with one charged lepton and jets from ppbar collisions at a center-of-mass
energy of 1.96 TeV. In these events, heavy flavor quarks from top quark decay
are identified with a secondary vertex tagging algorithm. From 162 pb-1 of data
collected by the Collider Detector at Fermilab, a total of 48 candidate events
are selected, where 13.5 +- 1.8 events are expected from background
contributions. We measure a ttbar production cross section of 5.6^{+1.2}_{-1.1}
(stat.) ^{+0.9}_{0.6} (syst.) pb.Comment: 28 pages, 20 figures. Published in Physical Review
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers âŒ99% of the euchromatic genome and is accurate to an error rate of âŒ1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
From Mendelâs discovery on pea to todayâs plant genetics and breeding
In 2015, we celebrated the 150th anniversary of the presentation of the seminal work of Gregor Johann Mendel. While Darwinâs theory of evolution was based on differential survival and differential reproductive success, Mendelâs theory of heredity relies on equality and stability throughout all stages of the life cycle. Darwinâs concepts were continuous variation and âsoftâ heredity; Mendel espoused discontinuous variation and âhardâ heredity. Thus, the combination of Mendelian genetics with Darwinâs theory of natural selection was the process that resulted in the modern synthesis of evolutionary biology. Although biology, genetics, and genomics have been revolutionized in recent years, modern genetics will forever rely on simple principles founded on pea breeding using seven single gene characters. Purposeful use of mutants to study gene function is one of the essential tools of modern genetics. Today, over 100 plant species genomes have been sequenced. Mapping populations and their use in segregation of molecular markers and markerâtrait association to map and isolate genes, were developed on the basis of Mendel's work. Genome-wide or genomic selection is a recent approach for the development of improved breeding lines. The analysis of complex traits has been enhanced by high-throughput phenotyping and developments in statistical and modeling methods for the analysis of phenotypic data. Introgression of novel alleles from landraces and wild relatives widens genetic diversity and improves traits; transgenic methodologies allow for the introduction of novel genes from diverse sources, and gene editing approaches offer possibilities to manipulate gene in a precise manner
Overpressure development in sedimentary basins induced by chemo-mechanical compaction of sandstones
A Landscape of Driver Mutations in Melanoma
Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic UV light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2), three of whichâRAC1, PPP6C, and STK19âharbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis.National Human Genome Research Institute (U.S.) (Large Scale Sequencing Program Grant U54 HG003067)Melanoma Research AllianceNational Cancer Institute (U.S.) (Support Grant CA-16672
Critical Conversations and A Call to Action!: A collective report from the June 2020 virtual gathering
Paul Kadetz - ORCID: 0000-0002-2824-1856 https://orcid.org/0000-0002-2824-1856Critical Conversations are held by members of the greater Engineering, Social Justice, and Peace network in the activist tradition of reflecting on our public engagement and collectively discovering ways of deepening our action. The particpants are selected based on their submissions (Expressions of Interest) in response to the Call for Participation in the Critcial Conversations disseminated through the ESJP website (esjp.org). For years, we have gathered in locations immersed in nature. In 2018 and 2019, the gathering took place in Cala Munda, organized by Caroline Baillie and Eric Feinblatt, in the beautiful Catskills mountains in upstate New York in the U.S.A.
We want to feel our connection with the land while we engage in critical conversations on the intersection of the engineering field with social justice and peace. Caroline Baillie facilitates these conversations employing forest pedagogy. Through this pedagogy, we open our hearts to the forest for seeking guidance on how our profession can help restore, heal, and serve people, planet, and life instead of its current practice of destroying, pillaging, and harming nature.
In the throes of the coronavirus pandemic, the urgency of action was evident in 2020 like never before. On June 26 and 27, 2020, a group of up to 40 educators, researchers, activists, and field practitioners, from 4 continents, met virtually for the 4th Annual Critical Conversations â almost thrice as large as the 2018 and 2019 groups that met in-person. The virtual format allowed for broader participation â both in numbers as well as geographical locations. Though we were physically separated in the online gathering, situated in our respective modern, often disconnected-from-nature enclaves, our hearts and minds were engaged in envisioning transition to a just and egalitarian society. In keeping with the need of the moment, our focus was on brainstorming action projects that we can implement in the near future. The retreat facilitated the formation of action teams, which spent the summer discussing possible action items moving forward. These teams are now looking for a more permanent structure with team leaders, team members, an infrastructure, and social media presence. This is a call to action!
We carried out these deliberations in an open-space format, wherein the agenda for the two days was set by the participants. In the two sessions on day one, using this participatory approach, we were able to sift six main themes that participants were interested in exploring in-depth. On day two, we divided ourselves into six teams and each team took a deeper dive into their theme of choice. Five of these teams have written summaries of their deliberations and proposed their Calls to Action for the engineering community, which we report below.https://doi.org/10.24908/ijesjp.v8i2.151578pubpub
Melanoma genome sequencing reveals frequent PREX2 mutations
Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5â55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)âa PTEN-interacting protein and negative regulator of PTEN in breast cancerâas a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.National Human Genome Research Institute (U.S.
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