38 research outputs found
Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges
- Author
- A Bauer-Mehren
- A Boorsma
- A Brazma
- A Shojaie
- A Subramanian
- AG Gilman
- AL Tarca
- AM Huerta
- Atul J. Butte
- B Efron
- B Mann
- B Zeeberg
- B Zeeberg
- B Zhang
- C Backes
- C Henegar
- C Perez-Iratxeta
- Christos A. Ouzounis
- CI Castillo-Davis
- D Maglott
- D Martin
- D Pennica
- DW Huang
- EI Boyle
- ET Wang
- F Al-Shahrour
- F Al-Shahrour
- G Bindea
- G Glazko
- G Joshi-Tope
- GF Berriz
- H Sun
- H Xiong
- I Dinu
- J Iqbal
- J Li
- J Rahnenführer
- J Ye
- JJ Goeman
- JJ Goeman
- KC Li
- KD Dahlquist
- L Beltrame
- L Klebanov
- L Tian
- La Martinez-Cruz
- M Ackermann
- M Brannon
- M Haertel-Wiesmann
- M Hummel
- M Kanehisa
- Marina Sirota
- MD Robinson
- ML Green
- OH Tam
- P Khatri
- P Khatri
- P Khatri
- P Pavlidis
- P Pavlidis
- PD Karp
- PD Thomas
- PK Majumder
- Purvesh Khatri
- Q Zheng
- R Braun
- R Breitling
- R Chen
- R Edgar
- RE Dolmetsch
- S Chiaretti
- S Draghici
- S Draghici
- S Drăghici
- SB Kim
- SE Calvano
- SW Doniger
- SW Kong
- SY Kim
- SY Rhee
- T Beissbarth
- T Breslin
- TR Golub
- U Mansmann
- VK Mootha
- WA Baumgartner Jr
- WT Barry
- Y Lu
- Ya Grigoryev
- Z Du
- Z Jiang
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2012
- Field of study
Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base–driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis
Pan-cancer analysis of whole genomes
- Author
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- Z. jq
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- Zenklusen
- Zeps
- zf Ghossein
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang H. b
- Zhao
- Zheng
- Zhou
- Zhou
- Zhu
- Zhu
- zi zj
- zm Jayaseelan
- Zou
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- zw Lewis
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- Publication date
- 11/12/2019
- Field of study
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
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- Abecasis GR
- Abecasis GR
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- Abyzov A
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- Anderson P
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- Ayub Q
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- Balasubramanian S
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- Batzer MA
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- Zhu H
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- Zhu J
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2012
- Field of study
By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations
Search for the Zγ decay mode of new high-mass resonances in pp collisions at s = 13 TeV with the ATLAS detector
- Author
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- Zhemchugov A
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- Åkesson TPA
- Öncel ÖO
- Ženiš T
- Živković L
- Publication venue
- Elsevier
- Publication date
- 01/12/2023
- Field of study
This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The
TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV
Pursuit of paired dijet resonances in the Run 2 dataset with ATLAS
- Author
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- Abidi SH
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- Castillo LRF
- Castro NF
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- Catmore JR
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- Zakareishvili T
- Zakharchuk N
- Zambito S
- Zang J
- Zanzi D
- Zaplatilek O
- Zeitnitz C
- Zeng H
- Zeng JC
- Zenger DT
- Zenin O
- Zenz S
- Zerradi S
- Zerwas D
- Zhai M
- Zhang B
- Zhang DF
- Zhang J
- Zhang J
- Zhang K
- Zhang L
- Zhang P
- Zhang R
- Zhang S
- Zhang S
- Zhang T
- Zhang X
- Zhang X
- Zhang Y
- Zhang Y
- Zhang Y
- Zhang Z
- Zhang Z
- Zhao H
- Zhao P
- Zhao T
- Zhao Y
- Zhao Z
- Zhemchugov A
- Zheng J
- Zheng K
- Zheng X
- Zheng Z
- Zhong D
- Zhou B
- Zhou H
- Zhou N
- Zhou Y
- Zhu CG
- Zhu J
- Zhu Y
- Zhu Y
- Zhuang X
- Zhukov K
- Zhulanov V
- Zimine NI
- Zinsser J
- Ziolkowski M
- Zoccoli A
- Zoch K
- Zorbas TG
- Zormpa O
- Zou W
- Zwalinski L
- Åkesson TPA
- Öncel ÖO
- Ženiš T
- Živković L
- Publication venue
- American Physical Society (APS)
- Publication date
- 01/01/2023
- Field of study
New particles with large masses that decay into hadronically interacting particles are predicted by many models of physics beyond the Standard Model. A search for a massive resonance that decays into pairs of dijet resonances is performed using..