Impact of Trisomy 8 on Expression of Genes Located on Chromosome 8 in Different AML Subgroups.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2034-2034
Author(s):  
Claudia Schoch ◽  
Wolfgang Kern ◽  
Alexander Kohlmann ◽  
Martin Dugas ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Dosage ◽  
Gene Expression Pattern ◽  
Chromosome 8 ◽  
Support Vector ◽  
Trisomy 8 ◽  
Gene Dosage Effect ◽  
Class Prediction ◽  
Expression Of Genes ◽  
The Impact

Abstract Trisomy 8 is the most frequently observed trisomy in acute myeloid leukemia (AML). It occurs as a sole karyotype abnormality or in addition to other chromosome aberrations. It was the aim of this study to analyze the impact of trisomy 8 on the expression of genes located on chromosome 8 in different AML subgroups. Therefore, gene expression analyses were performed in a total of 567 AML cases using Affymetrix U133A+B oligonucleotide microarrays. The following 14 subgroups were analyzed: +8 sole (n=19), +8 within a complex aberrant karyotype (n=11), +8 with t(15;17) (n=7), +8 and inv(16) (n=3), +8 with t(8;21) (n=3), +8 and 11q23/MLL (n=8), and +8 with other abnormalities (n=10). These were compared to 200 AML with normal karyotype and the following subgroups without trisomy 8: complex aberrant karyotype (n=73), t(15;17) (n=36), inv(16) (n=46), t(8;21) (n=37), 11q23/MLL (n=37), and other abnormalities (n=77). In total 1188 probe sets cover sequences located on chromosome 8 representing 580 genes. A significant higher mean expression of all genes located on chromosome 8 was observed in subgroups with +8 in comparison to their respective control groups (for all comparisons, p<0.05). Significantly higher expressed genes in groups with +8 in comparison to the respective groups without +8 were identified in all comparisons. The number of identified genes ranged from 40 in 11q23/MLL to 326 in trisomy 8 sole vs. normal. There was no common gene significantly overexpressed in all comparisons. Three genes (TRAM1, CHPPR, MGC40214) showed a significantly higher expression in 5 out of 7 comparisons. Between 19 and 107 genes with an exclusive overexpression in trisomy 8 cases in only one subtype comparison were identified. In addition, we performed class prediction using support vector machines (SVM) including all probe sets on the arrays. In one approach all 14 different subgroups were analyzed as one class each. Only 3 out of 61 cases with trisomy 8 were assigned into their correct subclass, while 40 cases were assigned to their corresponding genetic subclass without trisomy 8. In a second approach only two classes were defined: all cases with trisomy 8 combined vs. all cases without trisomy 8. Only 26 out of 61 (42.6%) with trisomy 8 were identified correctly underlining the fact that no distinct gene expression pattern is associated with trisomy 8 in general. Performing SVM only with genes located on chromosome 8 did not improve the correct assignment of cases with trisomy 8 overall. Only cases with trisomy 8 sole were correctly predicted in 58% as compared to 11% in SVM using all genes. In conclusion, overall the gain of chromosome 8 leads to a higher expression of genes located on chromosome 8. However, no consistent pattern of genes was identified which shows a higher expression in all AML subtypes with trisomy 8. This data suggest that the higher expression of genes located on chromosome 8 only in part is directly related to a gene dosage effect. Trisomy 8 may rather provide a platform for a higher expression of chromosome 8 genes which are specifically upregulated by accompanying genetic abnormalities in the respective AML subtypes. Therefore, trisomy 8 does not seem to be an abnormality determining specific disease characteristics such as the well known primary aberrations (t(8;21), inv(16), t(15;17), MLL/11q23) but rather a disease modulating secondary event in addition to primary cytogenetic or moleculargenetic aberrations.

Gene Expression Profiling of Hyperdiploid Multiple Reveal Complex Gene Dosage Effects and an mRNA Translation/Protein Synthesis Signature.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1538-1538
Author(s):  
Wee-Joo Chng ◽  
Scott Van Wier ◽  
Gregory Ahmann ◽  
Tammy Price-Troska ◽  
Kim Henderson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Differentially Expressed Genes ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Mrna Translation ◽  
Differentially Expressed ◽  
Gene Copy ◽  
Gene Dosage Effect ◽  
Expression Of Genes

Abstract Hyperdiploid MM (H-MM), characterized by recurrent trisomies constitute about 50% of MM, yet very little is known about its pathogenesis and oncogenic mechanisms. Studies in leukemia and solid tumors have shown gene dosage effect of aneuploidy on gene expression. To determine the possible gene dosage effect and deregulated cellular program in H-MM we undertook a gene expression study of CD138-enriched plasma-cell RNA from 53 hyperdiploid and 37 non-hyperdiploid MM (NH-MM) patients using the Affymetrix U133A chip (Affymetrix, Santa Clara, CA). Gene expression data was analyzed using GeneSpring 7 (Agilent Technologies, Palo Alto, CA). Genes differentially expressed between H-MM and NH-MM were obtained by t-test (p&lt;0.01). The majority of the differentially expressed genes (57%) were under-expressed in H-MM. Genes located on the commonly trisomic chromosomes were mostly (but not always) over-expressed in H-MM and constitute 76% of over-expressed genes. Chromosome 1 contained the most differentially expressed genes (17%) followed by chromosome 12 (9%), and 19 (8%). To examine the relationship of gene copy number to gene expression, we examined the expression of genes on chromosomes 9 and 15 in subjects with 2 copies (15 normal control and 20 NH-MM) and 3 copies (12 H-MM) of each chromosome as detected by interphase FISH. We then derived a ratio of the mean expression of each gene on these chromosomes between patients with 3 copies and 2 copies of the chromosome. If a simple relationship exists between gene expression and gene copy number, one would expect the ratio of expression of most genes on these two chromosomes to be about 1.5 in H-MM compared to NH-MM. However, many genes have ratios either higher than 2 or lower than 0.5. Furthermore, when the heterogeneity of cells with underlying trisomies is taken into consideration by correcting the ratio for the number of cells with trisomies, the actual ratio is always lower than the expected ratio. When the expression of genes on a chromosome was compressed to a median value, this value was always higher in the trisomic chromosomes for H-MM compared to NH-MM. The data suggests that although gene dosage influence gene expression, the relationship is complex and some genes are more gene dosage dependent than others. Amongst the differentially expressed genes with known function, 33% are involved in mRNA translation/protein synthesis. Of note, 37 of the top 100 differentially expressed genes are involved in these processes. In particular, 60 ribosomal protein (RP) genes are significantly (p&lt;0.05) upregulated in H-MM. This signature in H-MM is not associated with increase proliferation as measured by PCLI. This predominant signature suggests that deregulated protein synthesis may be important for the biology of H-MM. Many of these RPs are involved in the synthesis of product of oncogenic pathways (e.g. MYC, NF-KB pathways) and may mediate the growth and survival of tumor cells. It is therefore possible that these tumor cells may be sensitive to the disruption of mRNA translation/protein synthesis. Targeting the mTOR pathway with rapamycin may therefore be useful for treatment of H-MM.

scholarly journals Genomic imbalance determines positive and negative modulation of gene expression in diploid maize

2021 ◽  
Author(s):  
Xiaowen Shi ◽  
Hua Yang ◽  
Chen Chen ◽  
Jie Hou ◽  
Katherine M Hanson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Dosage ◽  
Leaf Tissue ◽  
Inverse Correlation ◽  
Rna Seq ◽  
Gene Dosage Effect ◽  
Genomic Imbalance ◽  
Common Effect ◽  
Modulation Of Gene Expression ◽  
The Impact

Abstract Genomic imbalance caused by changing the dosage of individual chromosomes (aneuploidy) has a more detrimental effect than varying the dosage of complete sets of chromosomes (ploidy). We examined the impact of both increased and decreased dosage of fifteen distal and one interstitial chromosomal regions via RNA-seq of maize (Zea mays) mature leaf tissue to reveal new aspects of genomic imbalance. The results indicate that significant changes in gene expression in aneuploids occur both on the varied chromosome (cis) and the remainder of the genome (trans), with a wider spread of modulation compared with the whole-ploidy series of haploid to tetraploid. In general, cis genes in aneuploids range from a gene-dosage effect to dosage compensation, whereas for trans genes the most common effect is an inverse correlation in that expression is modulated towards the opposite direction of the varied chromosomal dosage, although positive modulations also occur. Furthermore, this analysis revealed the existence of increased and decreased effects in which expression of many genes under genome imbalance are modulated towards the same direction regardless of increased or decreased chromosomal dosage, which is predicted from kinetic considerations of multicomponent molecular interactions. The findings provide novel insights into understanding mechanistic aspects of gene regulation.

scholarly journals Impact of Environmental Stressors on Gene Expression in the Embryo of the Italian Wall Lizard

2021 ◽  
Vol 11 (11) ◽  
pp. 4723
Author(s):  
Rosaria Scudiero ◽  
Chiara Maria Motta ◽  
Palma Simoniello
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Membrane Trafficking ◽  
Translational Regulation ◽  
Cellular Protection ◽  
Terrestrial Vertebrate ◽  
Expression Of Genes ◽  
Stress Changes ◽  
Probable Consequence ◽  
The Impact

The cleidoic eggs of oviparous reptiles are protected from the external environment by membranes and a parchment shell permeable to water and dissolved molecules. As a consequence, not only physical but also chemical insults can reach the developing embryos, interfering with gene expression. This review provides information on the impact of the exposure to cadmium contamination or thermal stress on gene expression during the development of Italian wall lizards of the genus Podarcis. The results obtained by transcriptomic analysis, although not exhaustive, allowed to identify some stress-reactive genes and, consequently, the molecular pathways in which these genes are involved. Cadmium-responsive genes encode proteins involved in cellular protection, metabolism and proliferation, membrane trafficking, protein interactions, neuronal transmission and plasticity, immune response, and transcription regulatory factors. Cold stress changes the expression of genes involved in transcriptional/translational regulation and chromatin remodeling and inhibits the transcription of a histone methyltransferase with the probable consequence of modifying the epigenetic control of DNA. These findings provide transcriptome-level evidence of how terrestrial vertebrate embryos cope with stress, giving a key to use in population survival and environmental change studies. A better understanding of the genes contributing to stress tolerance in vertebrates would facilitate methodologies and applications aimed at improving resistance to unfavourable environments.

scholarly journals Transversal gene expression panel to evaluate intestinal health in broiler chickens in different challenging conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Criado-Mesas ◽  
N. Abdelli ◽  
A. Noce ◽  
M. Farré ◽  
J. F. Pérez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Barrier Function ◽  
Nutrient Transport ◽  
Gene Expression Pattern ◽  
Vaccine Dose ◽  
Special Focus ◽  
Intestinal Health ◽  
Barrier Failure ◽  
Expression Of Genes

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.

Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 2090-2093 ◽  
Author(s):  
Dirk Kienle ◽  
Axel Benner ◽  
Alexander Kröber ◽  
Dirk Winkler ◽  
Daniel Mertens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Expression Of Genes ◽  
Vh Genes ◽  
Signaling Activation

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.

scholarly journals Effects of Laccaria bicolor on Gene Expression of Populus trichocarpa Root under Poplar Canker Stress

2021 ◽  
Vol 7 (12) ◽  
pp. 1024
Author(s):  
Fengxin Dong ◽  
Yihan Wang ◽  
Ming Tang
Keyword(s):  
Gene Expression ◽  
Disease Resistance ◽  
Plant Disease Resistance ◽  
Mycorrhizal Fungi ◽  
Populus Trichocarpa ◽  
Gene Expression Pattern ◽  
Oxygen Metabolism ◽  
Resistance Response ◽  
Expression Of Genes ◽  
Plant Pathogen Interaction

Poplars can be harmed by poplar canker. Inoculation with mycorrhizal fungi can improve the resistance of poplars to canker, but the molecular mechanism is still unclear. In this study, an aseptic inoculation system of L. bicolor–P. trichocarpa–B. dothidea was constructed, and transcriptome analysis was performed to investigate regulation by L. bicolor of the expression of genes in the roots of P. trichocarpa during the onset of B. dothidea infection, and a total of 3022 differentially expressed genes (DEGs) were identified. Weighted correlation network analysis (WGCNA) was performed on these DEGs, and 661 genes’ expressions were considered to be affected by inoculation with L. bicolor and B. dothidea. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these 661 DEGs were involved in multiple pathways such as signal transduction, reactive oxygen metabolism, and plant-pathogen interaction. Inoculation with L. bicolor changed the gene expression pattern of the roots, evidencing its involvement in the disease resistance response of P. trichocarpa. This research reveals the mechanism of L. bicolor in inducing resistance to canker of P. trichocarpa at the molecular level and provides a theoretical basis for the practical application of mycorrhizal fungi to improve plant disease resistance.

153 SUPPLEMENTATION WITH LINOLENIC ACID AND L-CARNITINE DURING IVM REDUCED THE EXPRESSION OF GENES RELATED TO LIPOGENESIS BUT DID NOT ALTER THE LIPID CONTENT AND CRYOTOLERANCE OF IN VITRO-PRODUCED EMBRYOS

2017 ◽  
Vol 29 (1) ◽  
pp. 185 ◽  
Author(s):  
B. C. S. Leao ◽  
N. A. S. Rocha Frigoni ◽  
P. C. Dall'Acqua ◽  
M. Ambrogi ◽  
G. B. Nunes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Linolenic Acid ◽  
Lipid Content ◽  
Control Group ◽  
Intracellular Lipid ◽  
Chi Square ◽  
Sudan Black B ◽  
Expression Of Genes ◽  
The Impact

This study was conducted to evaluate the impact of supplementation during in vitro maturation (IVM) with linolenic acid (ALA), l-carnitine (L-car), or the combination of both supplements on the embryo intracellular lipid content and cryotolerance, as well as in the embryo expression of genes involved in lipid metabolism (lipogenesis regulation: SCD1, FASN, and SREBP1; and β-oxidation pathway: CPT1B and CPT2). Cumulus-oocyte complexes (n = 1076) were IVM for 22 h at 38.5°C and 5% CO2 in air, in TCM-199 medium with bicarbonate, hormones, and 10% FCS (control group), supplemented with 100 μM ALA (ALA group), 5 mM L-car (L-car group), or a combination of 100 μM ALA + 5 mM L-car (ALA + L-car group). After IVF, presumptive zygotes were in vitro cultured in SOFaa medium supplemented with 5 mg mL−1 BSA and 2.5% FCS, at 38.5°C and 5% CO2 in air during 7 days. Cleavage and blastocyst rates were evaluated on Day 3 and 7, respectively (IVF = Day 0). At Day 7, the blastocysts were stained with the lipophilic dye Sudan Black B (n = 60), vitrified/warmed (n = 260; Ingámed® protocol, Maringa-PR, Brazil), or collected for analysis of gene expression (n = 180). Embryonic development were analysed by ANOVA and the multiple comparisons of means were determined by Tukey’s test. The embryonic re-expansion data were subjected to chi-square test and the differences in gene expression among groups were evaluated by Duncan’s multiple range test (P < 0.05). Data are presented as means ± standard error means. There was no effect (P > 0.05) of the supplements used during IVM on cleavage (79.54 ± 2.76% to 82.16 ± 1.13%) and blastocyst rates (29.03 ± 3.07% to 30.46 ± 2.01%). Similarly, the intracellular lipid content in Day-7 blastocysts (1.03 ± 0.04 to 1.15 ± 0.07 pixels) and the embryonic cryotolerance, assessed by the re-expansion rates after 24 h (67.3 to 78.3%) hatching rates after 48 h (11.5 to 25.5%) of post-warming culture, were unaffected (P > 0.05) by the supplements of IVM medium. Although the treatments did not alter (P > 0.05) the expression of CPT1B and CPT2 genes, the expression of FASN gene was decreased (P < 0.05) in the ALA group and the expression of SREBP1 gene was decreased (P < 0.05) in the ALA and L-car groups. The expression of the gene SCD1 was reduced (P < 0.05) in all treatments compared with the control group. Thus, despite the lack of effects of the treatments performed during IVM on the intracellular lipid content and cryotolerance of the embryos derived from the treated oocytes, a reduction in the expression of genes related to lipogenesis was observed in Day-7 blastocysts. These results suggest that treatments performed in the oocytes during IVM may have prolonged effects, affecting the subsequent expression of genes in embryos. Further studies are needed to determine the mechanisms related to the differentiation of the oocyte machinery during maturation. Financial support was provided by FAPESP (#2012/10084–4 and #2013/07382–6).

scholarly journals Circulating miRNA 887 is differentially expressed in ARDS and modulates endothelial function

2020 ◽  
Vol 318 (6) ◽  
pp. L1261-L1269 ◽  
Author(s):  
Andrew J. Goodwin ◽  
Pengfei Li ◽  
Perry V. Halushka ◽  
James A. Cook ◽  
Aman S. Sumal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
In Silico Analysis ◽  
Leukocyte Migration ◽  
Differentially Expressed ◽  
Expression Of Genes ◽  
Cell Gene Expression ◽  
And Function ◽  
The Impact

Circulating microRNAs (miRNAs) can be taken up by recipient cells and have been recently associated with the acute respiratory distress syndrome (ARDS). Their role in host predisposition to the syndrome is unknown. The objective of the study was to identify circulating miRNAs associated with the development of sepsis-related ARDS and examine their impact on endothelial cell gene expression and function. We determined miRNA levels in plasma collected from subjects during the first 24 h of admission to a tertiary intensive care unit for sepsis. A miRNA that was differentially expressed between subjects who did and did not develop ARDS was identified and was transfected into human pulmonary microvascular endothelial cells (HPMECs). RNA sequencing, in silico analysis, cytokine expression, and leukocyte migration assays were used to determine the impact of this miRNA on gene expression and cell function. In two cohorts, circulating miR-887-3p levels were elevated in septic patients who developed ARDS compared with those who did not. Transfection of miR-887-3p into HPMECs altered gene expression, including the upregulation of several genes previously associated with ARDS (e.g., CXCL10, CCL5, CX3CL1, VCAM1, CASP1, IL1B, IFNB, and TLR2), and activation of cellular pathways relevant to the response to infection. Functionally, miR-887-3p increased the endothelial release of chemokines and facilitated trans-endothelial leukocyte migration. Circulating miR-887-3p is associated with ARDS in critically ill patients with sepsis. In vitro, miR-887-3p regulates the expression of genes relevant to ARDS and neutrophil tracking. This miRNA may contribute to ARDS pathogenesis and could represent a novel therapeutic target.

Acute Myeloid Leukemia with Translocation t(8;16) Demonstrates Specific Cytomorphological, Cytogenetic, and Gene Expression Characteristics and Can Clearly Be Discriminated from Other AML with Balanced Translocations.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2897-2897
Author(s):  
Torsten Haferlach ◽  
Helmut Loeffler ◽  
Alexander Kohlmann ◽  
Martin Dugas ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Who Classification ◽  
De Novo ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Support Vector ◽  
Gene Expression Patterns ◽  
Down Regulation ◽  
Specific Expression ◽  
Balanced Translocations

Abstract Balanced chromosomal rearrangements leading to fusion genes on the molecular level define distinct biological subsets in AML. The four balanced rearrangements (t(15;17), t(8;21), inv(16), and 11q23/MLL) show a close correlation to cytomorphology and gene expression patterns. We here focused on seven AML with t(8;16)(p11;p13). This translocation is rare (7/3515 cases in own cohort). It is more frequently found in therapy-related AML than in de novo AML (3/258 t-AML, and 4/3287 de novo, p=0.0003). Cytomorphologically, AML with t(8;16) is characterized by striking features: In all 7 cases the positivity for myeloperoxidase on bone marrow smears was &gt;70% and intriguingly, in parallel &gt;80% of blast cells stained strongly positive for non-specific esterase (NSE) in all cases. Thus, these cases can not be classified according to FAB categories. These data suggest that AML-t(8;16) arise from a very early stem cell with both myeloid and monoblastic potential. Furthermore, we detected erythrophagocytosis in 6/7 cases that was described as specific feature in AML with t(8;16). Four pts. had chromosomal aberrations in addition to t(8;16), 3 of these were t-AML all showing aberrations of 7q. Survival was poor with 0, 1, 1, 2, 20 and 18+ (after alloBMT) mo., one lost to follow-up, respectively. We then analyzed gene expression patterns in 4 cases (Affymetrix U133A+B). First we compared t(8;16) AML with 46 AML FAB M1, 41 M4, 9 M5a, and 16 M5b, all with normal karyotype. Hierachical clustering and principal component analyses (PCA) revealed that t(8;16) AML were intercalating with FAB M4 and M5b and did not cluster near to M1. Thus, monocytic characteristics influence the gene expression pattern stronger than myeloid. Next we compared the t(8;16) AML with the 4 other balanced subtypes according to the WHO classification (t(15;17): 43; t(8;21): 40; inv(16): 49; 11q23/MLL-rearrangements: 50). Using support vector machines the overall accuracy for correct subgroup assignment was 97.3% (10-fold CV), and 96.8% (2/3 training and 1/3 test set, 100 runs). In PCA and hierarchical cluster analysis the t(8;16) were grouped in the vicinity of the 11q23 cases. However, in a pairwise comparison these two subgroups could be discriminated with an accuracy of 94.4% (10-fold CV). Genes with a specific expression in AML-t(8;16) were further investigated in pathway analyses (Ingenuity). 15 of the top 100 genes associated with AML-t(8;16) were involved in the CMYC-pathway with up regulation of BCOR, COXB5, CDK10, FLI1, HNRPA2B1, NSEP1, PDIP38, RAD50, SUPT5H, TLR2 and USP33, and down regulation of ERG, GATA2, NCOR2 and RPS20. CEBP beta, known to play a role in myelomonocytic differentiation, was also up-regulated in t(8;16)-AML. Ten additional genes out of the 100 top differentially expressed genes were also involved in this pathway with up-regulation of DDB2, HIST1H3D, NSAP1, PTPNS1, RAN, USP4, TRIM8, ZNF278 and down regulation of KIT and MBD2. In conclusion, AML with t(8;16) is a specific subtype of AML with unique characteristics in morphology and gene expression patterns. It is more frequently found in t-AML, outcome is inferior in comparison to other AML with balanced translocations. Due to its unique features, it is a candidate for inclusion into the WHO classification as a specific entity.

scholarly journals Improving the Interpretability of Classification Rules Discovered by an Ant Colony Algorithm: Extended Results

2016 ◽  
Vol 24 (3) ◽  
pp. 385-409 ◽  
Author(s):  
Fernando E. B. Otero ◽  
Alex A. Freitas
Keyword(s):  
Ant Colony Algorithm ◽  
Predictive Accuracy ◽  
Ant Colony ◽  
Support Vector ◽  
Classification Rules ◽  
Class Prediction ◽  
Vector Machines ◽  
Size Measure ◽  
The Impact

Most ant colony optimization (ACO) algorithms for inducing classification rules use a ACO-based procedure to create a rule in a one-at-a-time fashion. An improved search strategy has been proposed in the cAnt-Miner[Formula: see text] algorithm, where an ACO-based procedure is used to create a complete list of rules (ordered rules), i.e., the ACO search is guided by the quality of a list of rules instead of an individual rule. In this paper we propose an extension of the cAnt-Miner[Formula: see text] algorithm to discover a set of rules (unordered rules). The main motivations for this work are to improve the interpretation of individual rules by discovering a set of rules and to evaluate the impact on the predictive accuracy of the algorithm. We also propose a new measure to evaluate the interpretability of the discovered rules to mitigate the fact that the commonly used model size measure ignores how the rules are used to make a class prediction. Comparisons with state-of-the-art rule induction algorithms, support vector machines, and the cAnt-Miner[Formula: see text] producing ordered rules are also presented.

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