Browsing by Subject "SIGNATURES"

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  • Salmela, Heli; Stark, Taina; Stucki, Dimitri; Fuchs, Siiri; Freitak, Dalial; Dey, Alivia; Kent, Clement F.; Zayed, Amro; Dhaygude, Kishor; Hokkanen, Heikki; Sundstrom, Liselotte (2016)
    Protection against inflammation and oxidative stress is key in slowing down aging processes. The honey bee (Apis mellifera) shows flexible aging patterns linked to the social role of individual bees. One molecular factor associated with honey bee aging regulation is vitellogenin, a lipoglycophosphoprotein with anti-inflammatory and antioxidant properties. Recently, we identified three genes in Hymenopteran genomes arisen from ancient insect vitellogenin duplications, named vg-like-A, -B, and -C. The function of these vitellogenin homologs is unclear. We hypothesize that some of them might share gene-and protein-level similarities and a longevity-supporting role with vitellogenin. Here, we show how the structure and modifications of the vg-like genes and proteins have diverged from vitellogenin. Furthermore, all three vg-like genes show signs of positive selection, but the spatial location of the selected protein sites differ from those found in vitellogenin. We show that all these genes are expressed in both long-lived winter worker bees and in summer nurse bees with intermediate life expectancy, yet only vg-like-A shows elevated expression in winter bees as found in vitellogenin. Finally, we show that vg-like-A responds more strongly than vitellogenin to inflammatory and oxidative conditions in summer nurse bees, and that also vg-like-B responds to oxidative stress. We associate vg-like-A and, to lesser extent, vg-like-B to the antiaging roles of vitellogenin, but that vg-like-C probably is involved in some other function. Our analysis indicates that an ancient duplication event facilitated the adaptive and functional divergence of vitellogenin and its paralogs in the honey bee.
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T. (2018)
    The results of a previous search by the CMS Collaboration for squarks and gluinos are reinterpreted to constrain models of leptoquark (LQ) production. The search considers jets in association with a transverse momentum imbalance, using the M-T2 variable. The analysis uses proton-proton collision data at root s = 13 TeV, recorded with the CMS detector at the LHC in 2016 and corresponding to an integrated luminosity of 35.9 fb(-1). Leptoquark pair production is considered with LQ decays to a neutrino and a top, bottom, or light quark. This reinterpretation considers higher mass values than the original CMS search to constrain both scalar and vector LQs. Limits on the cross section for LQ pair production are derived at the 95% confidence level depending on the LQ decay mode. A vector LQ decaying with a 50% branching fraction to t nu, and 50% to b tau, has been proposed as part of an explanation of anomalous flavor physics results. In such a model, using only the decays to t nu, LQ masses below 1530 GeV are excluded assuming the Yang-Mills case with coupling kappa = 1, or 1115 GeV in the minimal coupling case kappa = 0, placing the most stringent constraint to date from pair production of vector LQs.
  • Palmerio, E.; Kilpua, E. K. J.; James, A. W.; Green, L. M.; Pomoell, J.; Isavnin, A.; Valori, G. (2017)
    A key aim in space weather research is to be able to use remote-sensing observations of the solar atmosphere to extend the lead time of predicting the geoeffectiveness of a coronal mass ejection (CME). In order to achieve this, the magnetic structure of the CME as it leaves the Sun must be known. In this article we address this issue by developing a method to determine the intrinsic flux rope type of a CME solely from solar disk observations. We use several well-known proxies for the magnetic helicity sign, the axis orientation, and the axial magnetic field direction to predict the magnetic structure of the interplanetary flux rope. We present two case studies: the 2 June 2011 and the 14 June 2012 CMEs. Both of these events erupted from an active region, and despite having clear in situ counterparts, their eruption characteristics were relatively complex. The first event was associated with an active region filament that erupted in two stages, while for the other event the eruption originated from a relatively high coronal altitude and the source region did not feature a filament. Our magnetic helicity sign proxies include the analysis of magnetic tongues, soft X-ray and/or extreme-ultraviolet sigmoids, coronal arcade skew, filament emission and absorption threads, and filament rotation. Since the inclination of the posteruption arcades was not clear, we use the tilt of the polarity inversion line to determine the flux rope axis orientation and coronal dimmings to determine the flux rope footpoints, and therefore, the direction of the axial magnetic field. The comparison of the estimated intrinsic flux rope structure to in situ observations at the Lagrangian point L1 indicated a good agreement with the predictions. Our results highlight the flux rope type determination techniques that are particularly useful for active region eruptions, where most geoeffective CMEs originate.
  • Alkodsi, Amjad; Cervera, Alejandra; Zhang, Kaiyang; Louhimo, Riku; Meriranta, Leo; Pasanen, Annika; Leivonen, Suvi-Katri; Holte, Harald; Leppä, Sirpa; Lehtonen, Rainer; Hautaniemi, Sampsa (2019)
    Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease whose personalized clinical management requires robust molecular stratification. Here, we show that somatic hypermutation (SHM) patterns constitute a marker for DLBCL molecular classification. The activity of SHM mutational processes delineated the cell of origin (COO) in DLBCL. Expression of the herein identified 36 SHM target genes stratified DLBCL into four novel SHM subtypes. In a meta-analysis of patients with DLBCL treated with immunochemotherapy, the SHM subtypes were significantly associated with overall survival (1642 patients) and progression-free survival (795 patients). Multivariate analysis of survival indicated that the prognostic impact of the SHM subtypes is independent from the COO classification and the International Prognostic Index. Furthermore, the SHM subtypes had a distinct clinical outcome within each of the COO subtypes, and strikingly, even within unclassified DLBCL. The genetic landscape of the four SHM subtypes indicated unique associations with driver alterations and oncogenic signaling in DLBCL, which suggests a possibility for therapeutic exploitation. These findings provide a biologically driven classification system in DLBCL with potential clinical applications.
  • Hanninen, Ulrika A.; Wirta, Erkki-Ville; Katainen, Riku; Tanskanen, Tomas; Hamberg, Jiri; Taipale, Minna; Böhm, Jan; Renkonen-Sinisalo, Laura; Lepistö, Anna; Forsström, Linda M.; Pitkänen, Esa; Palin, Kimmo; Seppälä, Toni T.; Mäkinen, Netta; Mecklin, Jukka-Pekka; Aaltonen, Lauri A. (2019)
    BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay between immune cell invasion and mutation profile in both lesions of an individual. RESULTS: The tumour pairs shared only few mutations, favouring different mutations in known CRC genes and signalling pathways and displayed variation in their signature content. Two tumour pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden. CONCLUSIONS: The study shows major diversity within SCRCs. Rather than rely on data from one tumour, our study highlights the need to evaluate both tumours of a synchronous pair for optimised targeted therapy.
  • Yadav, Bhagwan; Gopalacharyulu, Peddinti; Pemovska, Tea; Khan, Suleiman A.; Szwajda, Agnieszka; Tang, Jing; Wennerberg, Krister; Aittokallio, Tero (2015)
    Deconvoluting the molecular target signals behind observed drug response phenotypes is an important part of phenotype-based drug discovery and repurposing efforts. We demonstrate here how our network-based deconvolution approach, named target addiction score (TAS), provides insights into the functional importance of druggable protein targets in cell-based drug sensitivity testing experiments. Using cancer cell line profiling data sets, we constructed a functional classification across 107 cancer cell models, based on their common and unique target addiction signatures. The pan-cancer addiction correlations could not be explained by the tissue of origin, and only correlated in part with molecular and genomic signatures of the heterogeneous cancer cells. The TAS-based cancer cell classification was also shown to be robust to drug response data resampling, as well as predictive of the transcriptomic patterns in an independent set of cancer cells that shared similar addiction signatures with the 107 cancers. The critical protein targets identified by the integrated approach were also shown to have clinically relevant mutation frequencies in patients with various cancer subtypes, including not only well-established pan-cancer genes, such as PTEN tumor suppressor, but also a number of targets that are less frequently mutated in specific cancer types, including ABL1 oncoprotein in acute myeloid leukemia. An application to leukemia patient primary cell models demonstrated how the target deconvolution approach offers functional insights into patient-specific addiction patterns, such as those indicative of their receptor-type tyrosine-protein kinase FLT3 internal tandem duplication (FLT3-ITD) status and co-addiction partners, which may lead to clinically actionable, personalized drug treatment developments. To promote its application to the future drug testing studies, we have made available an open-source implementation of the TAS calculation in the form of a stand-alone R package.
  • Rajamäki, Kristiina; Taira, Aurora; Katainen, Riku; Välimäki, Niko; Kuosmanen, Anna; Plaketti, Roosa-Maria; Seppälä, Toni T.; Ahtiainen, Maarit; Wirta, Erkki-Ville; Vartiainen, Emilia; Sulo, Päivi; Ravantti, Janne; Lehtipuro, Suvi; Granberg, Kirsi J.; Nykter, Matti; Tanskanen, Tomas; Ristimäki, Ari; Koskensalo, Selja; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Taipale, Jussi; Mecklin, Jukka-Pekka; Aavikko, Mervi; Palin, Kimmo; Aaltonen, Lauri A. (2021)
    Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.
  • Vinuela, Ana; Varshney, Arushi; van de Bunt, Martijn; Prasad, Rashmi B.; Asplund, Olof; Bennett, Amanda; Boehnke, Michael; Brown, Andrew A.; Erdos, Michael R.; Fadista, Joao; Hansson, Ola; Hatem, Gad; Howald, Cedric; Iyengar, Apoorva K.; Johnson, Paul; Krus, Ulrika; MacDonald, Patrick E.; Mahajan, Anubha; Manning Fox, Jocelyn E.; Narisu, Narisu; Nylander, Vibe; Orchard, Peter; Oskolkov, Nikolay; Panousis, Nikolaos I.; Payne, Anthony; Stitzel, Michael L.; Vadlamudi, Swarooparani; Welch, Ryan; Collins, Francis S.; Mohlke, Karen L.; Gloyn, Anna L.; Scott, Laura J.; Dermitzakis, Emmanouil T.; Groop, Leif; Parker, Stephen C. J.; McCarthy, Mark I. (2020)
    Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.
  • Helle, Emmi; Ampuja, Minna; Dainis, Alexandra; Antola, Laura; Temmes, Elina; Tolvanen, Erik; Mervaala, Eero; Kivelä, Riikka (2021)
    Cell-cell interactions are crucial for organ development and function. In the heart, endothelial cells engage in bidirectional communication with cardiomyocytes regulating cardiac development and growth. We aimed to elucidate the organotypic development of cardiac endothelial cells and cardiomyocyte and endothelial cell crosstalk using human induced pluripotent stem cells (hiPSC). Single-cell RNA sequencing was performed with hiPSC-derived cardiomyocytes (hiPS-CMs) and endothelial cells (hiPS-ECs) in mono- and co-culture. The presence of hiPS-CMs led to increased expression of transcripts related to vascular development and maturation, cardiac development, as well as cardiac endothelial cell and endocardium-specific genes in hiPS-ECs. Interestingly, co-culture induced the expression of cardiomyocyte myofibrillar genes and MYL7 and MYL4 protein expression was detected in hiPS-ECs. Major regulators of BMP- and Notch-signaling pathways were induced in both cell types in co-culture. These results reflect the findings from animal studies and extend them to human endothelial cells, demonstrating the importance of EC-CM interactions during development.
  • Grandin, Maxime; Turc, Lucile; Battarbee, Markus; Ganse, Urs; Johlander, Andreas; Pfau-Kempf, Yann; Dubart, Maxime; Palmroth, Minna (2020)
    Particle precipitation is a central aspect of space weather, as it strongly couples the magnetosphere and the ionosphere and can be responsible for radio signal disruption at high latitudes. We present the first hybrid-Vlasov simulations of proton precipitation in the polar cusps. We use two runs from the Vlasiator model to compare cusp proton precipitation fluxes during southward and northward interplanetary magnetic field (IMF) driving. The simulations reproduce well-known features of cusp precipitation, such as a reverse dispersion of precipitating proton energies, with proton energies increasing with increasing geomagnetic latitude under northward IMF driving, and a nonreversed dispersion under southward IMF driving. The cusp is also found more polewards in the northward IMF simulation than in the southward IMF simulation. In addition, we find that the bursty precipitation during southward IMF driving is associated with the transit of flux transfer events in the vicinity of the cusp. In the northward IMF simulation, dual lobe reconnection takes place. As a consequence, in addition to the high-latitude precipitation spot associated with the lobe reconnection from the same hemisphere, we observe lower-latitude precipitating protons which originate from the opposite hemisphere's lobe reconnection site. The proton velocity distribution functions along the newly closed dayside magnetic field lines exhibit multiple proton beams travelling parallel and antiparallel to the magnetic field direction, which is consistent with previously reported observations with the Cluster spacecraft. In both runs, clear electromagnetic ion cyclotron waves are generated in the cusps and might further increase the calculated precipitating fluxes by scattering protons to the loss cone in the low-altitude cusp. Global kinetic simulations can improve the understanding of space weather by providing a detailed physical description of the entire near-Earth space and its internal couplings.
  • Järvinen, R.; Vainio, R.; Palmroth, M.; Juusola, L.; Hoilijoki, S.; Pfau-Kempf, Y.; Ganse, U.; Turc, L.; von Alfthan, S. (2018)
    We report ion acceleration by flux transfer events in the terrestrial magnetosheath in a global two-dimensional hybrid-Vlasov polar plane simulation of Earth's solar wind interaction. In the model we find that propagating flux transfer events created in magnetic reconnection at the dayside magnetopause drive fast-mode bow waves in the magnetosheath, which accelerate ions in the shocked solar wind flow. The acceleration at the bow waves is caused by a shock drift-like acceleration process under stationary solar wind and interplanetary magnetic field upstream conditions. Thus, the energization is not externally driven but results from plasma dynamics within the magnetosheath. Energetic proton populations reach the energy of 30 keV, and their velocity distributions resemble time-energy dispersive ion injections observed by the Cluster spacecraft in the magnetosheath.
  • Genome Aggregation Database Prod T; Genome Aggregation Database Consor; Wang, Qingbo; Pierce-Hoffman, Emma; Cummings, Beryl B.; MacArthur, Daniel G.; Groop, Leif; Färkkilä, Martti; Palotie, Aarno; Remes, Anne M.; Ripatti, Samuli; Salomaa, Veikko; Soininen, Hilkka; Suvisaari, Jaana; Tuomi, Tiinamaija; Vartiainen, Erkki; Wessman, Maija (2020)
    Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,792,248 MNVs across the genome with constituent variants falling within 2bp distance of one another, including 18,756 variants with a novel combined effect on protein sequence. Finally, we estimate the relative impact of known mutational mechanisms - CpG deamination, replication error by polymerase zeta, and polymerase slippage at repeat junctions - on the generation of MNVs. Our results demonstrate the value of haplotype-aware variant annotation, and refine our understanding of genome-wide mutational mechanisms of MNVs. Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.
  • Dodd, Matthew S.; Papineau, Dominic; Pirajno, Franco; Wan, Yusheng; Karhu, Juha A. (2019)
    The cycling of iron and organic matter (OM) is thought to have been a major biogeochemical cycle in the early ferruginous oceans which contributed to the deposition of banded iron formations (BIF). However, BIF are deficient in OM, which is postulated to be the result of near-complete oxidation of OM during iron reduction. We test this idea by documenting the prevalence of OM in clays within BIF and clays in shales associated with BIF. We find in shales >80% of OM occurs in clays, but
  • van der Kolk, Birgitta W.; Saari, Sina; Lovric, Alen; Arif, Muhammad; Alvarez, Marcus; Ko, Arthur; Miao, Zong; Sahebekhtiari, Navid; Muniandy, Maheswary; Heinonen, Sini; Oghabian, Ali; Jokinen, Riikka; Jukarainen, Sakari; Hakkarainen, Antti; Lundbom, Jesper; Kuula, Juho; Groop, Per-Henrik; Tukiainen, Taru; Lundbom, Nina; Rissanen, Aila; Kaprio, Jaakko; Williams, Evan G.; Zamboni, Nicola; Mardinoglu, Adil; Pajukanta, Paivi; Pietiläinen, Kirsi H. (2021)
    Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity.
  • Awad, Shady Adnan; Kankainen, Matti; Ojala, Teija; Koskenvesa, Perttu; Eldfors, Samuli; Ghimire, Bishwa; Kumar, Ashwini; Kytölä, Soili; Kamel, Mahmoud M.; Heckman, Caroline A.; Porkka, Kimmo; Mustjoki, Satu (2020)
    Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm accounting for similar to 15% of all leukemia. Progress of the disease from an indolent chronic phase to the more aggressive accelerated phase or blast phase (BP) occurs in a minority of cases and is associated with an accumulation of somatic mutations. We performed genetic profiling of 85 samples and transcriptome profiling of 12 samples from 59 CML patients. We identified recurrent somatic mutations in ABL1 (37%), ASXL1 (26%), RUNX1 (16%), and BCOR (16%) in the BP and observed that mutation signatures in the BP resembled those of acute myeloid leukemia (AML). We found that mutation load differed between the indolent and aggressive phases and that nonoptimal responders had more nonsilent mutations than did optimal responders at the time of diagnosis, as well as in follow-up. Using RNA sequencing, we identified other than BCR-ABL1 cancer-associated hybrid genes in 6 of the 7 BP samples. Uncovered expression alterations were in turn associated with mechanisms and pathways that could be targeted in CML management and by which somatic alterations may emerge in CML. Last, we showed the value of genetic data in CML management in a personalized medicine setting.
  • Fang, Hu; Barbour, Jayne A.; Poulos, Rebecca C.; Katainen, Riku; Aaltonen, Lauri A.; Wong, Jason W. H. (2020)
    Author summary Cancer arises through the accumulation of somatic mutations. The way that these somatic mutations form can vary greatly in different cancers. One of the most mutagenic processes that have been identified is caused by mutations within a replicative DNA polymerase known as Polymerase Epsilon (POLE). Cancers with such mutations present with hundreds of thousands of somatic mutations in their genome. Previous cancer genomics studies have identified a number of mutation hotspots in POLE, however how these different POLE mutants behave in affecting mutation distribution has not been studied. Here, we describe the genome-wide mutation profiles of distinct POLE mutant cancers. We find that different mutants indeed result in different mutation profiles and that this can be explained by the different fidelities of these mutants in replicating specific DNA sequences. Significantly, these differences have important implications in cancer formation as we found that a POLE mutation is strongly associated with a specific truncation of the TP53 cancer driver gene. This study furthers our understanding of the POLE mutagenic process in cancer and provide important insights into carcinogenesis in cancers with such mutations.
  • Davies, Emma E.; Forsyth, Robert J.; Good, Simon W.; Kilpua, Emilia K. J. (2020)
    We present observations of the same magnetic cloud made near Earth by the Advance Composition Explorer (ACE), Wind, and the Acceleration, Reconnection, Turbulence and Electrodynamics of the Moon's Interaction with the Sun (ARTEMIS) mission comprising the Time History of Events and Macroscale Interactions during Substorms (THEMIS) B and THEMIS C spacecraft, and later by Juno at a distance of 1.2 AU. The spacecraft were close to radial alignment throughout the event, with a longitudinal separation of 3.6 degrees between Juno and the spacecraft near Earth. The magnetic cloud likely originated from a filament eruption on 22 October 2011 at 00:05 UT, and caused a strong geomagnetic storm at Earth commencing on 24 October. Observations of the magnetic cloud at each spacecraft have been analysed using minimum variance analysis and two flux rope fitting models, Lundquist and Gold-Hoyle, to give the orientation of the flux rope axis. We explore the effect different trailing edge boundaries have on the results of each analysis method, and find a clear difference between the orientations of the flux rope axis at the near-Earth spacecraft and Juno, independent of the analysis method. The axial magnetic field strength and the radial width of the flux rope are calculated using both observations and fitting parameters and their relationship with heliocentric distance is investigated. Differences in results between the near-Earth spacecraft and Juno are attributed not only to the radial separation, but to the small longitudinal separation which resulted in a surprisingly large difference in the in situ observations between the spacecraft. This case study demonstrates the utility of Juno cruise data as a new opportunity to study magnetic clouds beyond 1 AU, and the need for caution in future radial alignment studies.
  • Campbell, Peter J.; Getz, Gad; Korbel, Jan O.; Stuart, Joshua M.; Jennings, Jennifer L.; Stein, Lincoln D.; Perry, Marc D.; Nahal-Bose, Hardeep K.; Ouellette, B. F. Francis; Li, Constance H.; Rheinbay, Esther; Nielsen, G. Petur; Sgroi, Dennis C.; Wu, Chin-Lee; Faquin, William C.; Deshpande, Vikram; Boutros, Paul C.; Lazar, Alexander J.; Hoadley, Katherine A.; Louis, David N.; Dursi, L. Jonathan; Yung, Christina; Bailey, Matthew H.; Saksena, Gordon; Raine, Keiran M.; Buchhalter, Ivo; Kleinheinz, Kortine; Schlesner, Matthias; Zhang, Junjun; Wang, Wenyi; Wheeler, David A.; Ding, Li; Simpson, Jared T.; O'Connor, Brian D.; Yakneen, Sergei; Ellrott, Kyle; Miyoshi, Naoki; Butler, Adam P.; Royo, Romina; Shorser, Solomon; Vazquez, Miguel; Rausch, Tobias; Tiao, Grace; Waszak, Sebastian M.; Rodriguez-Martin, Bernardo; Shringarpure, Suyash; Wu, Dai-Ying; Demidov, German M.; Delaneau, Olivier; Hayashi, Shuto; Imoto, Seiya; Habermann, Nina; Segre, Ayellet; Garrison, Erik; Cafferkey, Andy; Alvarez, Eva G.; Maria Heredia-Genestar, Jose; Muyas, Francesc; Drechsel, Oliver; Bruzos, Alicia L.; Temes, Javier; Zamora, Jorge; Baez-Ortega, Adrian; Kim, Hyung-Lae; Mashl, R. Jay; Ye, Kai; DiBiase, Anthony; Huang, Kuan-lin; Letunic, Ivica; McLellan, Michael D.; Newhouse, Steven J.; Shmaya, Tal; Kumar, Sushant; Wedge, David C.; Wright, Mark H.; Yellapantula, Venkata D.; Gerstein, Mark; Khurana, Ekta; Marques-Bonet, Tomas; Navarro, Arcadi; Bustamante, Carlos D.; Siebert, Reiner; Nakagawa, Hidewaki; Easton, Douglas F.; Ossowski, Stephan; Tubio, Jose M. C.; De La Vega, Francisco M.; Estivill, Xavier; Yuen, Denis; Mihaiescu, George L.; Omberg, Larsson; Ferretti, Vincent; Sabarinathan, Radhakrishnan; Pich, Oriol; Gonzalez-Perez, Abel; Weiner, Amaro Taylor; Fittall, Matthew W.; Demeulemeester, Jonas; Tarabichi, Maxime; Roberts, Nicola D.; Van Loo, Peter; Cortes-Ciriano, Isidro; Urban, Lara; Park, Peter; Bin Zhu, Lingli; Pitkaenen, Esa; Li, Yilong; Saini, Natalie; Klimczak, Leszek J.; Weischenfeldt, Joachim; Sidiropoulos, Nikos; Alexandrov, Ludmil B.; Rabionet, Raquel; Escaramis, Georgia; Bosio, Mattia; Holik, Aliaksei Z.; Susak, Hana; Prasad, Aparna; Erkek, Serap; Calabrese, Claudia; Raeder, Benjamin; Harrington, Eoghan; Mayes, Simon; Turner, Daniel; Juul, Sissel; Roberts, Steven A.; Song, Lei; Koster, Roelof; Mirabello, Lisa; Hua, Xing; Tanskanen, Tomas J.; Tojo, Marta; Chen, Jieming; Aaltonen, Lauri A.; Ratsch, Gunnar; Schwarz, Roland F.; Butte, Atul J.; Brazma, Alvis; Chanock, Stephen J.; Chatterjee, Nilanjan; Stegle, Oliver; Harismendy, Olivier; Bova, G. Steven; Gordenin, Dmitry A.; Haan, David; Sieverling, Lina; Feuerbach, Lars; Chalmers, Don; Joly, Yann; Knoppers, Bartha M.; Molnar-Gabor, Fruzsina; Phillips, Mark; Thorogood, Adrian; Townend, David; Goldman, Mary; Fonseca, Nuno A.; Xiang, Qian; Craft, Brian; Pineiro-Yanez, Elena; Munoz, Alfonso; Petryszak, Robert; Fullgrabe, Anja; Al-Shahrour, Fatima; Keays, Maria; Haussler, David; Weinstein, John; Huber, Wolfgang; Valencia, Alfonso; Papatheodorou, Irene; Zhu, Jingchun; Fan, Yu; Torrents, David; Bieg, Matthias; Chen, Ken; Chong, Zechen; Cibulskis, Kristian; Eils, Roland; Fulton, Robert S.; Gelpi, Josep L.; Gonzalez, Santiago; Gut, Ivo G.; Hach, Faraz; Heinold, Michael; Hu, Taobo; Huang, Vincent; Hutter, Barbara; Jaeger, Natalie; Jung, Jongsun; Kumar, Yogesh; Lalansingh, Christopher; Leshchiner, Ignaty; Livitz, Dimitri; Ma, Eric Z.; Maruvka, Yosef E.; Milovanovic, Ana; Nielsen, Morten Muhlig; Paramasivam, Nagarajan; Pedersen, Jakob Skou; Puiggros, Montserrat; Sahinalp, S. Cenk; Sarrafi, Iman; Stewart, Chip; Stobbe, Miranda D.; Wala, Jeremiah A.; Wang, Jiayin; Wendl, Michael C.; Werner, Johannes; Wu, Zhenggang; Xue, Hong; Yamaguchi, Takafumi N.; Yellapantula, Venkata; Davis-Dusenbery, Brandi N.; Grossman, Robert L.; Kim, Youngwook; Heinold, Michael C.; Hinton, Jonathan; Jones, David R.; Menzies, Andrew; Stebbings, Lucy; Hess, Julian M.; Rosenberg, Mara; Dunford, Andrew J.; Gupta, Manaswi; Imielinski, Marcin; Meyerson, Matthew; Beroukhim, Rameen; Reimand, Juri; Dhingra, Priyanka; Favero, Francesco; Dentro, Stefan C.; Wintersinger, Jeff; Rudneva, Vasilisa; Park, Ji Wan; Hong, Eun Pyo; Heo, Seong Gu; Kahles, Andre; Kjong-Van Lehmann,; Soulette, Cameron M.; Shiraishi, Yuichi; Liu, Fenglin; He, Yao; Demircioglu, Deniz; Davidson, Natalie R.; Greger, Liliana; Li, Siliang; Liu, Dongbing; Stark, Stefan G.; Zhang, Fan; Amin, Samirkumar B.; Bailey, Peter J.; Chateigner, Aurelien; Frenkel-Morgenstern, Milana; Hou, Yong; Huska, Matthew R.; Kilpinen, Helena; Lamaze, Fabien C.; Li, Chang; Li, Xiaobo; Li, Xinyue; Liu, Xingmin; Marin, Maximillian G.; Markowski, Julia; Nandi, Tannistha; Ojesina, Akinyemi; Pan-Hammarstrom, Qiang; Park, Peter J.; Pedamallu, Chandra Sekhar; Su, Hong; Tan, Patrick; Teh, Bin Tean; Wang, Jian; Xiong, Heng; Ye, Chen; Yung, Christina; Zhang, Xiuqing; Zheng, Liangtao; Zhu, Shida; Awadalla, Philip; Creighton, Chad J.; Wu, Kui; Yang, Huanming; Goke, Jonathan; Zhang, Zemin; Brooks, Angela N.; Martincorena, Inigo; Rubio-Perez, Carlota; Juul, Malene; Schumacher, Steven; Shapira, Ofer; Tamborero, David; Mularoni, Loris; Hornshoj, Henrik; Deu-Pons, Jordi; Muinos, Ferran; Bertl, Johanna; Guo, Qianyun; Bazant, Wojciech; Barrera, Elisabet; Al-Sedairy, Sultan T.; Aretz, Axel; Bell, Cindy; Betancourt, Miguel; Buchholz, Christiane; Calvo, Fabien; Chomienne, Christine; Dunn, Michael; Edmonds, Stuart; Green, Eric; Gupta, Shailja; Hutter, Carolyn M.; Jegalian, Karine; Jones, Nic; Lu, Youyong; Nakagama, Hitoshi; Nettekoven, Gerd; Planko, Laura; Scott, David; Shibata, Tatsuhiro; Shimizu, Kiyo; Stratton, Michael R.; Yugawa, Takashi; Tortora, Giampaolo; VijayRaghavan, K.; Zenklusen, Jean C.; Knoppers, Bartha M.; Aminou, Brice; Bartolome, Javier; Boroevich, Keith A.; Boyce, Rich; Buchanan, Alex; Byrne, Niall J.; Chen, Zhaohong; Cho, Sunghoon; Choi, Wan; Clapham, Peter; Dow, Michelle T.; Dursi, Lewis Jonathan; Eils, Juergen; Farcas, Claudiu; Fayzullaev, Nodirjon; Flicek, Paul; Heath, Allison P.; Hofmann, Oliver; Hong, Jongwhi H.; Hudson, Thomas J.; Huebschmann, Daniel; Ivkovic, Sinisa; Jeon, Seung-Hyup; Jiao, Wei; Kabbe, Rolf; Kerssemakers, Jules N. A.; Kim, Hyunghwan; Kim, Jihoon; Koscher, Michael; Koures, Antonios; Kovacevic, Milena; Lawerenz, Chris; Liu, Jia; Mijalkovic, Sanja; Mijalkovic-Lazic, Ana Mijalkovic; Miyano, Satoru; Nastic, Mia; Nicholson, Jonathan; Ocana, David; Ohi, Kazuhiro; Ohno-Machado, Lucila; Pihl, Todd D.; Prinz, Manuel; Radovic, Petar; Short, Charles; Sofia, Heidi J.; Spring, Jonathan; Struck, Adam J.; Tijanic, Nebojsa; Vicente, David; Wang, Zhining; Williams, Ashley; Woo, Youngchoon; Wright, Adam J.; Yang, Liming; Hamilton, Mark P.; Johnson, Todd A.; Kahraman, Abdullah; Kellis, Manolis; Polak, Paz; Sallari, Richard; Sinnott-Armstrong, Nasa; von Mering, Christian; Beltran, Sergi; Gerhard, Daniela S.; Gut, Marta; Trotta, Jean-Remi; Whalley, Justin P.; Niu, Beifang; Espiritu, Shadrielle M. G.; Gao, Shengjie; Huang, Yi; Lalansingh, Christopher M.; Teague, Jon W.; Wendl, Michael C.; Abascal, Federico; Bader, Gary D.; Bandopadhayay, Pratiti; Barenboim, Jonathan; Brunak, Soren; Fita, Joana Carlevaro; Chakravarty, Dimple; Chan, Calvin Wing Yiu; Choi, Jung Kyoon; Diamanti, Klev; Fink, J. Lynn; Frigola, Joan; Gambacorti-Passerini, Carlo; Garsed, Dale W.; Haradhvala, Nicholas J.; Harmanci, Arif O.; Helmy, Mohamed; Herrmann, Carl; Hobolth, Asger; Hodzic, Ermin; Hong, Chen; Isaev, Keren; Izarzugaza, Jose M. G.; Johnson, Rory; Juul, Randi Istrup; Kim, Jaegil; Kim, Jong K.; Komorowski, Jan; Lanzos, Andres; Larsson, Erik; Lee, Donghoon; Li, Shantao; Li, Xiaotong; Lin, Ziao; Liu, Eric Minwei; Lochovsky, Lucas; Lou, Shaoke; Madsen, Tobias; Marchal, Kathleen; Fundichely, Alexander Martinez; McGillivray, Patrick D.; Meyerson, William; Paczkowska, Marta; Park, Keunchil; Park, Kiejung; Pons, Tirso; Pulido-Tamayo, Sergio; Reyes Salazar, Iker; Reyna, Matthew A.; Rubin, Mark A.; Salichos, Leonidas; Sander, Chris; Schumacher, Steven E.; Shackleton, Mark; Shen, Ciyue; Shrestha, Raunak; Shuai, Shimin; Tsunoda, Tatsuhiko; Umer, Husen M.; Uuskula-Reimand, Liis; Verbeke, Lieven P. C.; Wadelius, Claes; Wadi, Lina; Warrell, Jonathan; Wu, Guanming; Yu, Jun; Zhang, Jing; Zhang, Xuanping; Zhang, Yan; Zhao, Zhongming; Zou, Lihua; Lawrence, Michael S.; Raphael, Benjamin J.; Bailey, Peter J.; Craft, David; Goldman, Mary J.; Aburatani, Hiroyuki; Binder, Hans; Dinh, Huy Q.; Heath, Simon C.; Hoffmann, Steve; Imbusch, Charles David; Kretzmer, Helene; Laird, Peter W.; Martin-Subero, Jose; Nagae, Genta; Shen, Hui; Wang, Qi; Weichenhan, Dieter; Zhou, Wanding; Berman, Benjamin P.; Brors, Benedikt; Plass, Christoph; Akdemir, Kadir C.; Bowtell, David D. L.; Burns, Kathleen H.; Busanovich, John; Chan, Kin; Dueso-Barroso, Ana; Edwards, Paul A.; Etemadmoghadam, Dariush; Haber, James E.; Jones, David T. W.; Ju, Young Seok; Kazanov, Marat D.; Koh, Youngil; Kumar, Kiran; Lee, Eunjung Alice; Lee, Jake June-Koo; Lynch, Andy G.; Macintyre, Geoff; Markowetz, Florian; Navarro, Fabio C. P.; Pearson, John; Rippe, Karsten; Scully, Ralph; Villasante, Izar; Waddell, Nicola; Yang, Lixing; Yao, Xiaotong; Yoon, Sung-Soo; Zhang, Cheng-Zhong; Bergstrom, Erik N.; Boot, Arnoud; Covington, Kyle; Fujimoto, Akihiro; Huang, Mi Ni; Islam, S. M. Ashiqul; McPherson, John R.; Morganella, Sandro; Mustonen, Ville; Ng, Alvin Wei Tian; Prokopec, Stephenie D.; Vazquez-Garcia, Ignacio; Wu, Yang; Yousif, Fouad; Yu, Willie; Rozen, Steven G.; Rudneva, Vasilisa A.; Shringarpure, Suyash S.; Turner, Daniel J.; Xia, Tian; Atwal, Gurnit; Chang, David K.; Cooke, Susanna L.; Faltas, Bishoy M.; Haider, Syed; Kaiser, Vera B.; Karlic, Rosa; Kato, Mamoru; Kubler, Kirsten; Margolin, Adam; Martin, Sancha; Nik-Zainal, Serena; P'ng, Christine; Semple, Colin A.; Smith, Jaclyn; Sun, Ren X.; Thai, Kevin; Wright, Derek W.; Yuan, Ke; Biankin, Andrew; Garraway, Levi; Grimmond, Sean M.; Adams, David J.; Anur, Pavana; Cao, Shaolong; Christie, Elizabeth L.; Cmero, Marek; Cun, Yupeng; Dawson, Kevin J.; Dentro, Stefan C.; Deshwar, Amit G.; Donmez, Nilgun; Drews, Ruben M.; Gerstung, Moritz; Ha, Gavin; Haase, Kerstin; Jerman, Lara; Ji, Yuan; Jolly, Clemency; Lee, Juhee; Lee-Six, Henry; Malikic, Salem; Mitchell, Thomas J.; Morris, Quaid D.; Oesper, Layla; Peifer, Martin; Peto, Myron; Rosebrock, Daniel; Rubanova, Yulia; Salcedo, Adriana; Sengupta, Subhajit; Shi, Ruian; Shin, Seung Jun; Spiro, Oliver; Vembu, Shankar; Wintersinger, Jeffrey A.; Yang, Tsun-Po; Yu, Kaixian; Zhu, Hongtu; Spellman, Paul T.; Weinstein, John N.; Chen, Yiwen; Fujita, Masashi; Han, Leng; Hasegawa, Takanori; Komura, Mitsuhiro; Li, Jun; Mizuno, Shinichi; Shimizu, Eigo; Wang, Yumeng; Xu, Yanxun; Yamaguchi, Rui; Yang, Fan; Yang, Yang; Yoon, Christopher J.; Yuan, Yuan; Liang, Han; Alawi, Malik; Borozan, Ivan; Brewer, Daniel S.; Cooper, Colin S.; Desai, Nikita; Grundhoff, Adam; Iskar, Murat; Su, Xiaoping; Zapatka, Marc; Lichter, Peter; Alsop, Kathryn; Bruxner, Timothy J. C.; Christ, Angelika N.; Cordner, Stephen M.; Cowin, Prue A.; Drapkin, Ronny; Fereday, Sian; George, Joshy; Hamilton, Anne; Holmes, Oliver; Hung, Jillian A.; Kassahn, Karin S.; Kazakoff, Stephen H.; Kennedy, Catherine J.; Leonard, Conrad R.; Mileshkin, Linda; Miller, David K.; Arnau, Gisela Mir; Mitchell, Chris; Newell, Felicity; Nones, Katia; Patch, Ann-Marie; Quinn, Michael C.; Taylor, Darrin F.; Thorne, Heather; Traficante, Nadia; Vedururu, Ravikiran; Waddell, Nick M.; Waring, Paul M.; Wood, Scott; Xu, Qinying; DeFazio, Anna; Anderson, Matthew J.; Antonello, Davide; Barbour, Andrew P.; Bassi, Claudio; Bersani, Samantha; Cataldo, Ivana; Chantrill, Lorraine A.; Chiew, Yoke-Eng; Chou, Angela; Cingarlini, Sara; Cloonan, Nicole; Corbo, Vincenzo; Davi, Maria Vittoria; Duthie, Fraser R.; Gill, Anthony J.; Graham, Janet S.; Harliwong, Ivon; Jamieson, Nigel B.; Johns, Amber L.; Kench, James G.; Landoni, Luca; Lawlor, Rita T.; Mafficini, Andrea; Merrett, Neil D.; Miotto, Marco; Musgrove, Elizabeth A.; Nagrial, Adnan M.; Oien, Karin A.; Pajic, Marina; Pinese, Mark; Robertson, Alan J.; Rooman, Ilse; Rusev, Borislav C.; Samra, Jaswinder S.; Scardoni, Maria; Scarlett, Christopher J.; Scarpa, Aldo; Sereni, Elisabetta; Sikora, Katarzyna O.; Simbolo, Michele; Taschuk, Morgan L.; Toon, Christopher W.; Vicentini, Caterina; Wu, Jianmin; Zeps, Nikolajs; Behren, Andreas; Burke, Hazel; Cebon, Jonathan; Dagg, Rebecca A.; De Paoli-Iseppi, Ricardo; Dutton-Regester, Ken; Field, Matthew A.; Fitzgerald, Anna; Hersey, Peter; Jakrot, Valerie; Johansson, Peter A.; Kakavand, Hojabr; Kefford, Richard F.; Lau, Loretta M. S.; Long, Georgina; Pickett, Hilda A.; Pritchard, Antonia L.; Pupo, Gulietta M.; Saw, Robyn P. M.; Schramm, Sarah-Jane; Shang, Catherine A.; Shang, Ping; Spillane, Andrew J.; Stretch, Jonathan R.; Tembe, Varsha; Thompson, John F.; Vilain, Ricardo E.; Wilmott, James S.; Yang, Jean Y.; Hayward, Nicholas K.; Mann, Graham J.; Scolyer, Richard A.; Bartlett, John; Bavi, Prashant; Chadwick, Dianne E.; Chan-Seng-Yue, Michelle; Cleary, Sean; Connor, Ashton A.; Czajka, Karolina; Denroche, Robert E.; Dhani, Neesha C.; Eagles, Jenna; Gallinger, Steven; Grant, Robert C.; Hedley, David; Hollingsworth, Michael A.; Jang, Gun Ho; Johns, Jeremy; Kalimuthu, Sangeetha; Liang, Sheng-Ben; Lungu, Ilinca; Luo, Xuemei; Mbabaali, Faridah; McPherson, Treasa A.; Miller, Jessica K.; Moore, Malcolm J.; Notta, Faiyaz; Pasternack, Danielle; Petersen, Gloria M.; Roehrl, Michael H. A.; Sam, Michelle; Selander, Iris; Serra, Stefano; Shahabi, Sagedeh; Thayer, Sarah P.; Timms, Lee E.; Wilson, Gavin W.; Wilson, Julie M.; Wouters, Bradly G.; McPherson, John D.; Beck, Timothy A.; Bhandari, Vinayak; Collins, Colin C.; Fleshner, Neil E.; Fox, Natalie S.; Fraser, Michael; Heisler, Lawrence E.; Lalonde, Emilie; Livingstone, Julie; Meng, Alice; Sabelnykova, Veronica Y.; Shiah, Yu-Jia; Van Der Kwast, Theodorus; Bristow, Robert G.; Ding, Shuai; Fan, Daiming; Li, Lin; Nie, Yongzhan; Xiao, Xiao; Xing, Rui; Yang, Shanlin; Yu, Yingyan; Zhou, Yong; Banks, Rosamonde E.; Bourque, Guillaume; Brennan, Paul; Letourneau, Louis; Riazalhosseini, Yasser; Scelo, Ghislaine; Vasudev, Naveen; Viksna, Juris; Lathrop, Mark; Tost, Jorg; Ahn, Sung-Min; Aparicio, Samuel; Arnould, Laurent; Aure, M. R.; Bhosle, Shriram G.; Birney, Ewan; Borg, Ake; Boyault, Sandrine; Brinkman, Arie B.; Brock, Jane E.; Broeks, Annegien; Borresen-Dale, Anne-Lise; Caldas, Carlos; Chin, Suet-Feung; Davies, Helen; Desmedt, Christine; Dirix, Luc; Dronov, Serge; Ehinger, Anna; Eyfjord, Jorunn E.; Fatima, Aquila; Foekens, John A.; Futreal, P. A.; Garred, Oystein; Giri, Dilip D.; Glodzik, Dominik; Grabau, Dorthe; Hilmarsdottir, Holmfridur; Hooijer, Gerrit K.; Jacquemier, Jocelyne; Jang, Se Jin; Jonasson, Jon G.; Jonkers, Jos; Kim, Hyung-Yong; King, Tari A.; Knappskog, Stian; Kong, Gu; Krishnamurthy, Savitri; Lakhani, Sunil R.; Langerod, Anita; Larsimont, Denis; Lee, Hee Jin; Lee, Jeong-Yeon; Lee, Ming Ta Michael; Lingjaerde, Ole Christian; MacGrogan, Gaetan; Martens, John W. M.; O'Meara, Sarah; Pauporte, Iris; Pinder, Sarah; Pivot, Xavier; Provenzano, Elena; Purdie, Colin A.; Ramakrishna, Manasa; Ramakrishnan, Kamna; Reis-Filho, Jorge; Richardson, Andrea L.; Ringner, Markus; Rodriguez, Javier Bartolome; Rodriguez-Gonzalez, F. German; Romieu, Gilles; Salgado, Roberto; Sauer, Torill; Shepherd, Rebecca; Sieuwerts, Anieta M.; Simpson, Peter T.; Smid, Marcel; Sotiriou, Christos; Span, Paul N.; Stefansson, Olafur Andri; Stenhouse, Alasdair; Stunnenberg, Henk G.; Sweep, Fred; Tan, Benita Kiat Tee; Thomas, Gilles; Thompson, Alastair M.; Tommasi, Stefania; Treilleux, Isabelle; Tutt, Andrew; Ueno, Naoto T.; Van Laere, Steven; Van den Eynden, Gert G.; Vermeulen, Peter; Viari, Alain; Vincent-Salomon, Anne; Wong, Bernice H.; Yates, Lucy; Zou, Xueqing; van Deurzen, Carolien H. M.; van de Vijver, Marc J.; van't Veer, Laura; Ammerpohl, Ole; Aukema, Sietse; Bergmann, Anke K.; Bernhart, Stephan H.; Borkhardt, Arndt; Borst, Christoph; Burkhardt, Birgit; Claviez, Alexander; Goebler, Maria Elisabeth; Haake, Andrea; Haas, Siegfried; Hansmann, Martin; Hoell, Jessica; Hummel, Michael; Karsch, Dennis; Klapper, Wolfram; Kneba, Michael; Kreuz, Markus; Kube, Dieter; Kueppers, Ralf; Lenze, Dido; Loeffler, Markus; Lopez, Cristina; Mantovani-Loeffler, Luisa; Moeller, Peter; Ott, German; Radlwimmer, Bernhard; Richter, Julia; Rohde, Marius; Rosenstiel, Philip C.; Rosenwald, Andreas; Schilhabel, Markus B.; Schreiber, Stefan; Stadler, Peter F.; Staib, Peter; Stilgenbauer, Stephan; Sungalee, Stephanie; Szczepanowski, Monika; Toprak, Umut H.; Truemper, Lorenz H. P.; Wagener, Rabea; Zenz, Thorsten; Hovestadt, Volker; von Kalle, Christof; Kool, Marcel; Korshunov, Andrey; Landgraf, Pablo; Lehrach, Hans; Northcott, Paul A.; Pfister, Stefan M.; Reifenberger, Guido; Warnatz, Hans-Joerg; Wolf, Stephan; Yaspo, Marie-Laure; Assenov, Yassen; Gerhauser, Clarissa; Minner, Sarah; Schlomm, Thorsten; Simon, Ronald; Sauter, Guido; Sueltmann, Holger; Biswas, Nidhan K.; Maitra, Arindam; Majumder, Partha P.; Sarin, Rajiv; Barbi, Stefano; Bonizzato, Giada; Cantu, Cinzia; Dei Tos, Angelo P.; Fassan, Matteo; Grimaldi, Sonia; Luchini, Claudio; Malleo, Giuseppe; Marchegiani, Giovanni; Milella, Michele; Paiella, Salvatore; Pea, Antonio; Pederzoli, Paolo; Ruzzenente, Andrea; Salvia, Roberto; Sperandio, Nicola; Arai, Yasuhito; Hama, Natsuko; Hiraoka, Nobuyoshi; Hosoda, Fumie; Nakamura, Hiromi; Ojima, Hidenori; Okusaka, Takuji; Totoki, Yasushi; Urushidate, Tomoko; Fukayama, Masashi; Ishikawa, Shumpei; Katai, Hitoshi; Katoh, Hiroto; Komura, Daisuke; Rokutan, Hirofumi; Saito-Adachi, Mihoko; Suzuki, Akihiro; Taniguchi, Hirokazu; Tatsuno, Kenji; Ushiku, Tetsuo; Yachida, Shinichi; Yamamoto, Shogo; Aikata, Hiroshi; Arihiro, Koji; Ariizumi, Shun-ichi; Chayama, Kazuaki; Furuta, Mayuko; Gotoh, Kunihito; Hayami, Shinya; Hirano, Satoshi; Kawakami, Yoshiiku; Maejima, Kazuhiro; Nakamura, Toru; Nakano, Kaoru; Ohdan, Hideki; Sasaki-Oku, Aya; Tanaka, Hiroko; Ueno, Masaki; Yamamoto, Masakazu; Yamaue, Hiroki; Choo, Su Pin; Cutcutache, Ioana; Khuntikeo, Narong; Ong, Choon Kiat; Pairojkul, Chawalit; Popescu, Irinel; Ahn, Keun Soo; Aymerich, Marta; Lopez-Guillermo, Armando; Lopez-Otin, Carlos; Puente, Xose S.; Campo, Elias; Amary, Fernanda; Baumhoer, Daniel; Behjati, Sam; Bjerkehagen, Bodil; Futreal, P. A.; Myklebost, Ola; Pillay, Nischalan; Tarpey, Patrick; Tirabosco, Roberto; Zaikova, Olga; Flanagan, Adrienne M.; Boultwood, Jacqueline; Bowen, David T.; Cazzola, Mario; Green, Anthony R.; Hellstrom-Lindberg, Eva; Malcovati, Luca; Nangalia, Jyoti; Papaemmanuil, Elli; Vyas, Paresh; Ang, Yeng; Barr, Hugh; Beardsmore, Duncan; Eldridge, Matthew; Gossage, James; Grehan, Nicola; Hanna, George B.; Hayes, Stephen J.; Hupp, Ted R.; Khoo, David; Lagergren, Jesper; Lovat, Laurence B.; MacRae, Shona; O'Donovan, Maria; O'Neill, J. Robert; Parsons, Simon L.; Preston, Shaun R.; Puig, Sonia; Roques, Tom; Sanders, Grant; Sothi, Sharmila; Tavare, Simon; Tucker, Olga; Turkington, Richard; Underwood, Timothy J.; Welch, Ian; Fitzgerald, Rebecca C.; Berney, Daniel M.; De Bono, Johann S.; Cahill, Declan; Camacho, Niedzica; Dennis, Nening M.; Dudderidge, Tim; Edwards, Sandra E.; Fisher, Cyril; Foster, Christopher S.; Ghori, Mohammed; Gill, Pelvender; Gnanapragasam, Vincent J.; Gundem, Gunes; Hamdy, Freddie C.; Hawkins, Steve; Hazell, Steven; Howat, William; Isaacs, William B.; Karaszi, Katalin; Kay, Jonathan D.; Khoo, Vincent; Kote-Jarai, Zsofia; Kremeyer, Barbara; Kumar, Pardeep; Lambert, Adam; Leongamornlert, Daniel A.; Livni, Naomi; Lu, Yong-Jie; Luxton, Hayley J.; Marsden, Luke; Massie, Charlie E.; Matthews, Lucy; Mayer, Erik; McDermott, Ultan; Merson, Sue; Neal, David E.; Ng, Anthony; Nicol, David; Ogden, Christopher; Rowe, Edward W.; Shah, Nimish C.; Thomas, Sarah; Thompson, Alan; Verrill, Clare; Visakorpi, Tapio; Warren, Anne Y.; Whitaker, Hayley C.; Zhang, Hongwei; van As, Nicholas; Eeles, Rosalind A.; Abeshouse, Adam; Agrawal, Nishant; Akbani, Rehan; Al Ahmadie, Hikmat; Albert, Monique; Aldape, Kenneth; Ally, Adrian; Appelbaum, Elizabeth L.; Armenia, Joshua; Asa, Sylvia; Auman, J. Todd; Balasundaram, Miruna; Balu, Saianand; Barnholtz-Sloan, Jill; Bathe, Oliver F.; Baylin, Stephen B.; Benz, Christopher; Berchuck, Andrew; Berrios, Mario; Bigner, Darell; Birrer, Michael; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S.; Bosenberg, Marcus; Bowlby, Reanne; Boyd, Jeffrey; Broaddus, Russell R.; Brock, Malcolm; Brooks, Denise; Bullman, Susan; Caesar-Johnson, Samantha J.; Carey, Thomas E.; Carlsen, Rebecca; Cerfolio, Robert; Chandan, Vishal S.; Chen, Hsiao-Wei; Cherniack, Andrew D.; Chien, Jeremy; Cho, Juok; Chuah, Eric; Cibulskis, Carrie; Cope, Leslie; Cordes, Matthew G.; Curley, Erin; Czerniak, Bogdan; Danilova, Ludmila; Davis, Ian J.; Defreitas, Timothy; Demchok, John A.; Dhalla, Noreen; Dhir, Rajiv; Doddapaneni, HarshaVardhan; El-Naggar, Adel; Felau, Ina; Ferguson, Martin L.; Finocchiaro, Gaetano; Fong, Kwun M.; Frazer, Scott; Friedman, William; Fronick, Catrina C.; Fulton, Lucinda A.; Gabriel, Stacey B.; Gao, Jianjiong; Gehlenborg, Nils; Gershenwald, Jeffrey E.; Ghossein, Ronald; Giama, Nasra H.; Gibbs, Richard A.; Gomez, Carmen; Govindan, Ramaswamy; Hayes, D. Neil; Hegde, Apurva M.; Heiman, David; Heins, Zachary; Hepperla, Austin J.; Holbrook, Andrea; Holt, Robert A.; Hoyle, Alan P.; Hruban, Ralph H.; Hu, Jianhong; Huang, Mei; Huntsman, David; Huse, Jason; Donahue, Christine A. Iacobuzio; Ittmann, Michael; Jayaseelan, Joy C.; Jefferys, Stuart R.; Jones, Corbin D.; Jones, Steven J. M.; Juhl, Hartmut; Kang, Koo Jeong; Karlan, Beth; Kasaian, Katayoon; Kebebew, Electron; Kim, Hark Kyun; Korchina, Viktoriya; Kundra, Ritika; Lai, Phillip H.; Lander, Eric; Le, Xuan; Lee, Darlene; Levine, Douglas A.; Lewis, Lora; Ley, Tim; Li, Haiyan Irene; Lin, Pei; Linehan, W. M.; Liu, Fei Fei; Lu, Yiling; Lype, Lisa; Ma, Yussanne; Maglinte, Dennis T.; Mardis, Elaine R.; Marks, Jeffrey; Marra, Marco A.; Matthew, Thomas J.; Mayo, Michael; McCune, Karen; Meier, Samuel R.; Meng, Shaowu; Mieczkowski, Piotr A.; Mikkelsen, Tom; Miller, Christopher A.; Mills, Gordon B.; Moore, Richard A.; Morrison, Carl; Mose, Lisle E.; Moser, Catherine D.; Mungall, Andrew J.; Mungall, Karen; Mutch, David; Muzny, Donna M.; Myers, Jerome; Newton, Yulia; Noble, Michael S.; O'Donnell, Peter; O'Neill, Brian Patrick; Ochoa, Angelica; Park, Joong-Won; Parker, Joel S.; Pass, Harvey; Pastore, Alessandro; Pennell, Nathan A.; Perou, Charles M.; Petrelli, Nicholas; Potapova, Olga; Rader, Janet S.; Ramalingam, Suresh; Rathmell, W. Kimryn; Reuter, Victor; Reynolds, Sheila M.; Ringel, Matthew; Roach, Jeffrey; Roberts, Lewis R.; Robertson, A. Gordon; Sadeghi, Sara; Saller, Charles; Sanchez-Vega, Francisco; Schadendorf, Dirk; Schein, Jacqueline E.; Schmidt, Heather K.; Schultz, Nikolaus; Seethala, Raja; Senbabaoglu, Yasin; Shelton, Troy; Shi, Yan; Shih, Juliann; Shmulevich, Ilya; Shriver, Craig; Signoretti, Sabina; Simons, Janae; Singer, Samuel; Sipahimalani, Payal; Skelly, Tara J.; McCune, Karen Smith; Socci, Nicholas D.; Soloway, Matthew G.; Sood, Anil K.; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Thiessen, Nina; Thompson, R. Houston; Thorne, Leigh B.; Tsao, Ming; Umbricht, Christopher; Van Den Berg, David J.; Van Meir, Erwin G.; Veluvolu, Umadevi; Voet, Douglas; Wang, Linghua; Weinberger, Paul; Weisenberger, Daniel J.; Wigle, Dennis; Wilkerson, Matthew D.; Wilson, Richard K.; Winterhoff, Boris; Wiznerowicz, Maciej; Wong, Tina; Wong, Winghing; Xi, Liu; Yau, Christina; Zhang, Hailei; Zhang, Hongxin; Zhang, Jiashan (2020)
    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).
  • Leinonen, Jussi; Lebsock, Matthew D.; Tanelli, Simone; Sy, Ousmane O.; Dolan, Brenda; Chase, Randy J.; Finlon, Joseph A.; von Lerber, Annakaisa; Moisseev, Dmitri (2018)
    We have developed an algorithm that retrieves the size, number concentration and density of falling snow from multifrequency radar observations. This work builds on previous studies that have indicated that three-frequency radars can provide information on snow density, potentially improving the accuracy of snow parameter estimates. The algorithm is based on a Bayesian framework, using lookup tables mapping the measurement space to the state space, which allows fast and robust retrieval. In the forward model, we calculate the radar reflectivities using recently published snow scattering databases. We demonstrate the algorithm using multifrequency airborne radar observations from the OLYMPEX-RADEX field campaign, comparing the retrieval results to hydrometeor identification using ground-based polarimetric radar and also to collocated in situ observations made using another aircraft. Using these data, we examine how the availability of multiple frequencies affects the retrieval accuracy, and we test the sensitivity of the algorithm to the prior assumptions. The results suggest that multifrequency radars are substantially better than single-frequency radars at retrieving snow microphysical properties. Meanwhile, triple-frequency radars can retrieve wider ranges of snow density than dual-frequency radars and better locate regions of highdensity snow such as graupel, although these benefits are relatively modest compared to the difference in retrieval performance between dual- and single-frequency radars. We also examine the sensitivity of the retrieval results to the fixed a priori assumptions in the algorithm, showing that the multi-frequency method can reliably retrieve snowflake size, while the retrieved number concentration and density are affected significantly by the assumptions.
  • Awad, Shady Adnan; Dufva, Olli; Ianevski, Aleksandr; Ghimire, Bishwa; Koski, Jan; Maliniemi, Pilvi; Thomson, Daniel; Schreiber, Andreas; Heckman, Caroline A.; Koskenvesa, Perttu; Korhonen, Matti; Porkka, Kimmo; Branford, Susan; Aittokallio, Tero; Kankainen, Matti; Mustjoki, Satu (2021)
    Blast-phase chronic myeloid leukemia (BP-CML) is associated with additional chromosomal aberrations,RUNX1mutations being one of the most common. Tyrosine kinase inhibitor therapy has only limited efficacy in BP-CML, and characterization of more defined molecular subtypes is warranted in order to design better treatment modalities for this poor prognosis patient group. Using whole-exome and RNA sequencing we demonstrate thatPHF6andBCORL1mutations,IKZF1deletions, and AID/RAG-mediated rearrangements are enriched inRUNX1(mut)BP-CML leading to typical mutational signature. On transcriptional level interferon and TNF signaling were deregulated in primaryRUNX1(mut)CML cells and stem cell and B-lymphoid factors upregulated giving a rise to distinct phenotype. This was accompanied with the sensitivity ofRUNX1(mut)blasts to CD19-CAR T cells in ex vivo assays. High-throughput drug sensitivity and resistance testing revealed leukemia cells fromRUNX1(mut)patients to be highly responsive for mTOR-, BCL2-, and VEGFR inhibitors and glucocorticoids. These findings were further investigated and confirmed in CRISPR/Cas9-edited homozygousRUNX1(-/-)and heterozygousRUNX1(-/mut)BCR-ABL positive cell lines. Overall, our study provides insights into the pathogenic role ofRUNX1mutations and highlights personalized targeted therapy and CAR T-cell immunotherapy as potentially promising strategies for treatingRUNX1(mut)BP-CML patients.