Browsing by Subject "GENOME"

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  • Kallio, M. Aleksi; Tuimala, Jarno T.; Hupponen, Taavi; Klemela, Petri; Gentile, Massimiliano; Scheinin, Ilari; Koski, Mikko; Kaki, Janne; Korpelainen, Eija I. (2011)
  • Tukiainen, Taru; Pirinen, Matti; Sarin, Antti-Pekka; Ladenvall, Claes; Kettunen, Johannes; Lehtimaeki, Terho; Lokki, Marja-Liisa; Perola, Markus; Sinisalo, Juha; Vlachopoulou, Efthymia; Eriksson, Johan G.; Groop, Leif; Jula, Antti; Jaervelin, Marjo-Riitta; Raitakari, Olli T.; Salomaa, Veikko; Ripatti, Samuli (2014)
  • Klymiuk, Valentina; Yaniv, Elitsur; Huang, Lin; Raats, Dina; Fatiukha, Andrii; Chen, Shisheng; Feng, Lihua; Frenkel, Zeev; Krugman, Tamar; Lidzbarsky, Gabriel; Chang, Wei; Jääskeläinen, Marko J.; Schudoma, Christian; Paulin, Lars; Laine, Pia; Bariana, Harbans; Sela, Hanan; Saleem, Kamran; Sorensen, Chris Khadgi; Hovmoller, Mogens S.; Distelfeld, Assaf; Chalhoub, Boulos; Dubcovsky, Jorge; Korol, Abraham B.; Schulman, Alan H.; Fahima, Tzion (2018)
    Yellow rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating fungal disease threatening much of global wheat production. Race-specific resistance (R)-genes are used to control rust diseases, but the rapid emergence of virulent Pst races has prompted the search for a more durable resistance. Here, we report the cloning of Yr15, a broad-spectrum R-gene derived from wild emmer wheat, which encodes a putative kinase-pseudokinase protein, designated as wheat tandem kinase 1, comprising a unique R-gene structure in wheat. The existence of a similar gene architecture in 92 putative proteins across the plant kingdom, including the barley RPG1 and a candidate for Ug8, suggests that they are members of a distinct family of plant proteins, termed here tandem kinase-pseudokinases (TKPs). The presence of kinase-pseudokinase structure in both plant TKPs and the animal Janus kinases sheds light on the molecular evolution of immune responses across these two kingdoms.
  • Le Bras, Yvan; Collin, Olivier; Monjeaud, Cyril; Lacroix, Vincent; Rivals, Eric; Lemaitre, Claire; Miele, Vincent; Sacomoto, Gustavo; Marchet, Camille; Cazaux, Bastien; El Aabidine, Amal Zine; Salmela, Leena; Alves-Carvalho, Susete; Andrieux, Alexan; Uricaru, Raluca; Peterlongo, Pierre (2016)
    Background: With next-generation sequencing (NGS) technologies, the life sciences face a deluge of raw data. Classical analysis processes for such data often begin with an assembly step, needing large amounts of computing resources, and potentially removing or modifying parts of the biological information contained in the data. Our approach proposes to focus directly on biological questions, by considering raw unassembled NGS data, through a suite of six command-line tools. Findings: Dedicated to 'whole-genome assembly-free' treatments, the Colib'read tools suite uses optimized algorithms for various analyses of NGS datasets, such as variant calling or read set comparisons. Based on the use of a de Bruijn graph and bloom filter, such analyses can be performed in a few hours, using small amounts of memory. Applications using real data demonstrate the good accuracy of these tools compared to classical approaches. To facilitate data analysis and tools dissemination, we developed Galaxy tools and tool shed repositories. Conclusions: With the Colib'read Galaxy tools suite, we enable a broad range of life scientists to analyze raw NGS data. More importantly, our approach allows the maximum biological information to be retained in the data, and uses a very low memory footprint.
  • Jalanka, Jonna; Cheng, Jing; Hiippala, Kaisa; Ritari, Jarmo; Salojärvi, Jarkko; Ruuska, Tarja; Kalliomaki, Marko; Satokari, Reetta (2020)
    Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n= 26) and non-IBD controls (n= 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA,p= 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.
  • Daly, Paul; Peng, Mao; Mitchell, Hugh D.; Kim, Young-Mo; Ansong, Charles; Brewer, Heather; de Gijsel, Peter; Lipton, Mary S.; Markillie, Lye Meng; Nicora, Carrie D.; Orr, Galya; Wiebenga, Ad; Hilden, Kristiina S.; Kabel, Mirjam A.; Baker, Scott E.; Makela, Miia R.; de Vries, Ronald P. (2020)
    Saprobic fungi, such as Aspergillus niger, grow as colonies consisting of a network of branching and fusing hyphae that are often considered to be relatively uniform entities in which nutrients can freely move through the hyphae. In nature, different parts of a colony are often exposed to different nutrients. We have investigated, using a multi-omics approach, adaptation of A. niger colonies to spatially separated and compositionally different plant biomass substrates. This demonstrated a high level of intra-colony differentiation, which closely matched the locally available substrate. The part of the colony exposed to pectin-rich sugar beet pulp and to xylan-rich wheat bran showed high pectinolytic and high xylanolytic transcript and protein levels respectively. This study therefore exemplifies the high ability of fungal colonies to differentiate and adapt to local conditions, ensuring efficient use of the available nutrients, rather than maintaining a uniform physiology throughout the colony.
  • Bösl, Korbinian; Ianevski, Aleksandr; Than, Thoa T.; Andersen, Petter I.; Kuivanen, Suvi; Teppor, Mona; Zusinaite, Eva; Dumpis, Uga; Vitkauskiene, Astra; Cox, Rebecca J.; Kallio-Kokko, Hannimari; Bergqvist, Anders; Tenson, Tanel; Merits, Andres; Oksenych, Valentyn; Bjørås, Magnar; Anthonsen, Marit W.; Shum, David; Kaarbø, Mari; Vapalahti, Olli; Windisch, Marc P.; Superti-Furga, Giulio; Snijder, Berend; Kainov, Denis; Kandasamy, Richard K. (2019)
    Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
  • Miyauchi, Shingo; Hage, Hayat; Drula, Elodie; Lesage-Meessen, Laurence; Berrin, Jean-Guy; Navarro, David; Favel, Anne; Chaduli, Delphine; Grisel, Sacha; Haon, Mireille; Piumi, Francois; Levasseur, Anthony; Lomascolo, Anne; Ahrendt, Steven; Barry, Kerrie; LaButti, Kurt M.; Chevret, Didier; Daum, Chris; Mariette, Jerome; Klopp, Christophe; Cullen, Daniel; de Vries, Ronald P.; Gathman, Allen C.; Hainaut, Matthieu; Henrissat, Bernard; Hilden, Kristiina S.; Kuees, Ursula; Lilly, Walt; Lipzen, Anna; Maekelae, Miia R.; Martinez, Angel T.; Morel-Rouhier, Melanie; Morin, Emmanuelle; Pangilinan, Jasmyn; Ram, Arthur F. J.; Woesten, Han A. B.; Ruiz-Duenas, Francisco J.; Riley, Robert; Record, Eric; Grigoriev, Igor; Rosso, Marie-Noelle (2020)
    White-rot (WR) fungi are pivotal decomposers of dead organic matter in forest ecosystems and typically use a large array of hydrolytic and oxidative enzymes to deconstruct lignocellulose. However, the extent of lignin and cellulose degradation may vary between species and wood type. Here, we combined comparative genomics, transcriptomics and secretome proteomics to identify conserved enzymatic signatures at the onset of wood-decaying activity within the Basidiomycota genus Pycnoporus. We observed a strong conservation in the genome structures and the repertoires of protein-coding genes across the four Pycnoporus species described to date, despite the species having distinct geographic distributions. We further analysed the early response of P. cinnabarinus, P. coccineus and P. sanguineus to diverse (ligno)-cellulosic substrates. We identified a conserved set of enzymes mobilized by the three species for breaking down cellulose, hemicellulose and pectin. The co-occurrence in the exo-proteomes of H2O2-producing enzymes with H2O2-consuming enzymes was a common feature of the three species, although each enzymatic partner displayed independent transcriptional regulation. Finally, cellobiose dehydrogenase-coding genes were systematically co-regulated with at least one AA9 lytic polysaccharide monooxygenase gene, indicative of enzymatic synergy in vivo. This study highlights a conserved core white-rot fungal enzymatic mechanism behind the wood-decaying process.
  • Palin, Kimmo; Pitkänen, Esa; Turunen, Mikko; Sahu, Biswajyoti; Pihlajamaa, Päivi; Kivioja, Teemu; Kaasinen, Eevi; Välimäki, Niko; Hänninen, Ulrika A.; Cajuso, Tatiana; Aavikko, Mervi; Tuupanen, Sari; Kilpivaara, Outi; van den Berg, Linda; Kondelin, Johanna; Tanskanen, Tomas; Katainen, Riku; Grau, Marta; Rauanheimo, Heli; Plaketti, Roosa-Maria; Taira, Aurora; Sulo, Päivi; Hartonen, Tuomo; Dave, Kashyap; Schmierer, Bernhard; Botla, Sandeep; Sokolova, Maria; Vähärautio, Anna; Gladysz, Kornelia; Ongen, Halit; Dermitzakis, Emmanouil; Bramsen, Jesper Bertram; Orntoft, Torben Falck; Andersen, Claus Lindbjerg; Ristimäki, Ari; Lepistö, Anna; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Taipale, Jussi; Aaltonen, Lauri A. (2018)
    Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (Al) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible Al targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within Al peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of Al. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between Al target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of Al in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
  • Thi Phuong Nam Bui,; Manneras-Holm, Louise; Puschmann, Robert; Wu, Hao; Troise, Antonio Dario; Nijsse, Bart; Boeren, Sjef; Backhed, Fredrik; Fiedler, Dorothea; deVos, Willem M. (2021)
    Here, the authors report an anaerobic metabolic pathway from the dominant gut butyrogen Anaerostipes, showing several strains of this genus to be capable of producing propionate from dietary myo-inositol that associates with reduced fasting-glucose levels in mice. We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [C-13]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifying 3-oxoacid CoA transferase as a key enzyme involved in both 3-oxopropionyl-CoA and propionate formation. This pathway also allowed conversion of phytate-derived inositol into propionate as shown with [C-13]-phytate in fecal samples amended with A. rhamnosivorans. Metabolic and (meta)genomic analyses explained the adaptation of Anaerostipes spp. to inositol-containing substrates and identified a propionate-production gene cluster to be inversely associated with metabolic biomarkers in (pre)diabetes cohorts. Co-administration of myo-inositol with live A. rhamnosivorans in western-diet fed mice reduced fasting-glucose levels comparing to heat-killed A. rhamnosivorans after 6-weeks treatment. Altogether, these data suggest a potential beneficial role for intestinal Anaerostipes spp. in promoting host health.
  • Tsuiko, O.; Noukas, M.; Zilina, O.; Hensen, K.; Tapanainen, J. S.; Magi, R.; Kals, M.; Kivistik, P. A.; Haller-Kikkatalo, K.; Salumets, A.; Kurg, A. (2016)
    Can spontaneous premature ovarian failure (POF) patients derived from population-based biobanks reveal the association between copy number variations (CNVs) and POF? CNVs can hamper the functional capacity of ovaries by disrupting key genes and pathways essential for proper ovarian function. POF is defined as the cessation of ovarian function before the age of 40 years. POF is a major reason for female infertility, although its cause remains largely unknown. The current retrospective CNV study included 301 spontaneous POF patients and 3188 control individuals registered between 2003 and 2014 at Estonian Genome Center at the University of Tartu (EGCUT) biobank. DNA samples from 301 spontaneous POF patients were genotyped by Illumina HumanCoreExome (258 samples) and HumanOmniExpress (43 samples) BeadChip arrays. Genotype and phenotype information was drawn from the EGCUT for the 3188 control population samples, previously genotyped with HumanCNV370 and HumanOmniExpress BeadChip arrays. All identified CNVs were subjected to functional enrichment studies for highlighting the POF pathogenesis. Real-time quantitative PCR was used to validate a subset of CNVs. Whole-exome sequencing was performed on six patients carrying hemizygous deletions that encompass genes essential for meiosis or folliculogenesis. Eleven novel microdeletions and microduplications that encompass genes relevant to POF were identified. For example, FMN2 (1q43) and SGOL2 (2q33.1) are essential for meiotic progression, while TBP (6q27), SCARB1 (12q24.31), BNC1 (15q25) and ARFGAP3 (22q13.2) are involved in follicular growth and oocyte maturation. The importance of recently discovered hemizygous microdeletions of meiotic genes SYCE1 (10q26.3) and CPEB1 (15q25.2) in POF patients was also corroborated. This is a descriptive analysis and no functional studies were performed. Anamnestic data obtained from population-based biobank lacked clinical, biological (hormone levels) or ultrasonographical data, and spontaneous POF was predicted retrospectively by excluding known extraovarian causes for premature menopause. The present study, with high number of spontaneous POF cases, provides novel data on associations between the genomic aberrations and premature menopause of ovarian cause and demonstrates that population-based biobanks are powerful source of biological samples and clinical data to reveal novel genetic lesions associated with human reproductive health and disease, including POF. This study was supported by the Estonian Ministry of Education and Research (IUT20-43, IUT20-60, IUT34-16, SF0180027s10 and 9205), Enterprise Estonia (EU30020 and EU48695), Eureka's EUROSTARS programme (NOTED, EU41564), grants from European Union's FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, SARM, |EU324509) and Horizon 2020 innovation programme (WIDENLIFE, 692065), Academy of Finland and the Sigrid Juselius Foundation.
  • Markussen, Trine; Happel, Elisabeth M.; Teikari, Jonna Emilia; Huchaiah, Vimala; Alneberg, Johannes; Andersson, Anders F.; Sivonen, Anna Kaarina; Riemann, Lasee; Middelboe, Mathias; Kisand, Veljo (2018)
    Bacteria are major drivers of biogeochemical nutrient cycles and energy fluxes in marine environments, yet how bacterial communities respond to environ- mental change is not well known. Metagenomes allow examination of genetic responses of the entire micro- bial community to environmental change. However, it is challenging to link metagenomes directly to bio- geochemical process rates. Here, we investigate metagenomic responses in natural bacterioplankton communities to simulated environmental stressors in the Baltic Sea, including increased river water input, increased nutrient concentration, and reduced oxy- gen level. This allowed us to identify informative pro- karyotic gene markers, responding to environmental perturbation. Our results demonstrate that metage- nomic and metabolic changes in bacterial communi- ties in response to environmental stressors are influenced both by the initial community composition and by the biogeochemical factors shaping the func- tional response. Furthermore, the different sources of dissolved organic matter (DOM) had the largest impact on metagenomic blueprint. Most prominently, changes in DOM loads influenced specific trans- porter types reflecting the substrate availability and DOC assimilation and consumption pathways. The results provide new knowledge for developing models of ecosystem structure and biogeochemical cycling in future climate change scenarios and advance our exploration of the potential use of marine microorganisms as markers for environmen- tal conditions.
  • Schmierer, Bernhard; Botla, Sandeep K.; Zhang, Jilin; Turunen, Mikko; Kivioja, Teemu; Taipale, Jussi (2017)
    Loss-of-function screening by CRISPR/Cas9 gene knockout with pooled, lentiviral guide libraries is a widely applicable method for systematic identification of genes contributing to diverse cellular phenotypes. Here, Random Sequence Labels (RSLs) are incorporated into the guide library, which act as unique molecular identifiers (UMIs) to allow massively parallel lineage tracing and lineage dropout screening. RSLs greatly improve the reproducibility of results by increasing both the precision and the accuracy of screens. They reduce the number of cells needed to reach a set statistical power, or allow a more robust screen using the same number of cells.
  • Kovanen, Leena; Kaunisto, Mari; Donner, Kati; Saarikoski, Sirkku T.; Partonen, Timo (2013)
  • Choi, Jaeyoung; Kim, Ki-Tae; Huh, Aram; Kwon, Seomun; Hong, Changyoung; Asiegbu, Fred O.; Jeon, Junhyun; Lee, Yong-Hwan (2015)
    Over the past two decades, epigenetics has evolved into a key concept for understanding regulation of gene expression. Among many epigenetic mechanisms, covalent modifications such as acetylation and methylation of lysine residues on core histones emerged as a major mechanism in epigenetic regulation. Here, we present the database for histone-modifying enzymes (dbHiMo; aimed at facilitating functional and comparative analysis of histone-modifying enzymes (HMEs). HMEs were identified by applying a search pipeline built upon profile hidden Markov model (HMM) to proteomes. The database incorporates 11 576 HMEs identified from 603 proteomes including 483 fungal, 32 plants and 51 metazoan species. The dbHiMo provides users with web-based personalized data browsing and analysis tools, supporting comparative and evolutionary genomics. With comprehensive data entries and associated web-based tools, our database will be a valuable resource for future epigenetics/epigenomics studies.
  • Meriranta, Leo; Pasanen, Annika; Louhimo, Riku; Cervera, Alejandra; Alkodsi, Amjad; Autio, Matias; Taskinen, Minna; Rantanen, Ville; Karjalainen-Lindsberg, Marja-Liisa; Holte, Harald; Delabie, Jan; Lehtonen, Rainer; Hautaniemi, Sampsa; Leppä, Sirpa (2017)
  • Safronov, Omid; Kreuzwieser, Juergen; Haberer, Georg; Alyousif, Mohamed S.; Schulze, Waltraud; Al-Harbi, Naif; Arab, Leila; Ache, Peter; Stempfl, Thomas; Kruse, Joerg; Mayer, Klaus X.; Hedrich, Rainer; Rennenberg, Heinz; Salojarvi, Jarkko; Kangasjarvi, Jaakko (2017)
    Plants adapt to the environment by either long-term genome evolution or by acclimatization processes where the cellular processes and metabolism of the plant are adjusted within the existing potential in the genome. Here we studied the adaptation strategies in date palm, Phoenix dactylifera, under mild heat, drought and combined heat and drought by transcriptomic and metabolomic profiling. In transcriptomics data, combined heat and drought resembled heat response, whereas in metabolomics data it was more similar to drought. In both conditions, soluble carbohydrates, such as fucose, and glucose derivatives, were increased, suggesting a switch to carbohydrate metabolism and cell wall biogenesis. This result is consistent with the evidence from transcriptomics and cis-motif analysis. In addition, transcriptomics data showed transcriptional activation of genes related to reactive oxygen species in all three conditions (drought, heat, and combined heat and drought), suggesting increased activity of enzymatic antioxidant systems in cytosol, chloroplast and peroxisome. Finally, the genes that were differentially expressed in heat and combined heat and drought stresses were significantly enriched for circadian and diurnal rhythm motifs, suggesting new stress avoidance strategies.
  • Li, Shitian; Ramakrishnan, Muthusamy; Vinod, K. K.; Kalendar, Ruslan; Yrjälä, Kim; Zhou, Mingbing (2020)
    Bamboo, a non-timber grass species, known for exceptionally fast growth, is a commercially viable crop. Long terminal repeat (LTR) retrotransposons, the main class I mobile genetic elements in plant genomes, are highly abundant (46%) in bamboo contributing to genome diversity. They play significant roles in the regulation of gene expression, chromosome size and structure as well as in genome integrity. Inter-retrotransposon amplified polymorphism (IRAP) is a high-throughput method to study the genetic diversity of plant species. Till date, there are no markers based on Transposable Elements (TEs) for the bamboo genome and no reports on bamboo genetic diversity using the IRAP method. Phyllostachys is an Asian bamboo, the largest group in the bamboo subfamily, Bambusoideae, and it is of great economic value due to its fast growth. The structure of LTR-retrotransposon superfamilies, Ty3-gypsy and Ty1-copia, were analysed in the bamboo genome using LTRharvest and LTRdigest software. A total of 98,850 LTR retrotransposons with both ends of intact LTR sequences were identified, grouped into 64,281 clusters/scaffolds, using CD-HIT software. Among the total of 64,281 clusters, 13 clusters had more than 30 copy numbers of LTR sequences and at least one copy had all intact protein domains such as gag protein and polyprotein. Based on the high copy numbers of conserved LTR sequences, a total of 16 IRAP primers were developed. All these IRAP primers were used to study the genetic diversity and population structure of the Asian bamboo. AMOVA analysis was done for 58 Asian bamboo species collected from nine different provinces of China, from Italy and America. In the bamboo species, these IRAP primers produced a total of 3340 amplicons with an average of 98% polymorphism. The 58 Asian bamboo species were grouped into two major clusters and four sub-clusters, based on UPGMA analysis. UPGMA cluster analysis was corroborated by statistical analyses of genetic similarity coefficients. Structure analysis showed that the bamboo species could be divided into four subpopulations (K = 4): SP1, SP2, SP3 and SP4. All SPs had an admixture of alleles. AMOVA analysis showed that higher genetic variations occurred within populations (75%) rather than among populations (25%). The study highlights the usability of IRAP in Asian bamboo to determine inter-species variability using retrotransposon markers.
  • Sharma, Himanshu; Hyvönen, Jaakko; Poczai, Péter (2020)
    Premise Plant invasions are increasing globally, and extensive study of the genetic background of the source and invading populations is needed to understand such biological processes. For this reason, chloroplast microsatellite markers were identified to explore the genetic diversity of the noxious weed Ambrosia trifida (Asteraceae). Methods and Results The complete chloroplast genome of A. trifida was mined for microsatellite loci, and 15 novel chloroplast primers were identified to assess the genetic diversity of 49 Ambrosia samples. The number of alleles amplified ranged from two to six, with an average of 3.2 alleles per locus. Shannon's information index varied from 0.305 and 1.467, expected heterozygosity ranged from 0.178 to 0.645, and the polymorphism information content value ranged from 0.211 to 0.675 (average 0.428). The cross-species transferability of the 15 microsatellite loci was also evaluated in four related Ambrosia species (A. artemisiifolia, A. maritima, A. psilostachya, and A. tenuifolia). Conclusions The novel chloroplast microsatellite markers developed in the current study demonstrate substantial cross-species transferability and will be helpful in future genetic diversity studies of A. trifida and related species.
  • 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.