| 1. |
- Lindqvist, C. Mårten, et al.
(författare)
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Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:39, s. 64071-64088
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Tidskriftsartikel (refereegranskat)abstract
- To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
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| 2. |
- Adoue, Veronique, et al.
(författare)
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Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs
- 2014
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292 .- 1744-4292. ; 10:10, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.
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| 3. |
- Almlöf, Jonas, et al.
(författare)
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A short and efficient error correcting code for polarization coded photonic qubits in a dissipative channel
- 2011
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Ingår i: Optics Communications. - : Elsevier BV. - 0030-4018 .- 1873-0310. ; 284:1, s. 550-554
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Tidskriftsartikel (refereegranskat)abstract
- We propose a short and efficient non-degenerate quantum error correcting code that is adapted for qubits encoded on two orthogonal, single-photon states (e.g., horizontally and vertically polarized) subject to a dissipative channel. The proposed code draws its strength from the fact that it is adapted to the physical characteristics of the information-carrying basis states under the action of the channel. The code combines different energy manifolds and consists of only 3 spatio-temporal modes and on average 2 photons per code word.
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| 4. |
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| 5. |
- Almlöf, Jonas Carlsson, et al.
(författare)
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Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e52260-
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.
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| 6. |
- Almlöf, Jonas Carlsson, et al.
(författare)
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Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus
- 2019
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Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 138:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare (0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported.
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| 7. |
- Almlöf, Jonas, et al.
(författare)
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Creating and detecting specious randomness
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present a new test of non-randomness that tests both the lower and the upper critical limit of aχ2-statistic. While checking the upper critical value has been employed by other tests, we argue that also the lower critical value should be examined for non-randomness. To this end, we prepare a binary sequence where all possible bit strings of a certain length occurs the same number of times and demonstrate that such sequences pass a well-known suite of tests for non-randomness. We show that such sequences can be compressed, and therefore are somewhat predictable and thus not fully random. The presented test can detect such non-randomness, and its novelty rests on analysing fixed-length bit string frequencies that lie closer to the a priori probabilities than could be expected by chance
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| 8. |
- Almlöf, Jonas, et al.
(författare)
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Fidelity as a figure of merit in quantum error correction
- 2013
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Ingår i: Quantum information & computation. - 1533-7146. ; 13:1-2, s. 0009-0020
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the fidelity as a figure of merit in quantum error correction schemes. We show that when identifiable but uncorrectable errors occur as a result of the action of the channel, a common strategy that improves the fidelity actually decreases the transmitted mutual information. The conclusion is that while the fidelity is simple to calculate and therefore often used, it is perhaps not always a recommendable figure of merit for quantum error correction. The reason is that while it roughly speaking encourages optimisation of the "mean probability of success", it gives no incentive for a protocol to indicate exactly where the errors lurk. For small error probabilities, the latter information is more important for the integrity of the information than optimising the mean probability of success.
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| 9. |
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| 10. |
- Almlöf, Jonas
(författare)
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Quantum error correction
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Quantum error correction is the art of protecting quantum states from the detrimental influence from the environment. To master this art, one must understand how the system interacts with the environment and gives rise to a full set of quantum phenomena, many of which have no correspondence in classical information theory. Such phenomena include decoherence, an effect that in general destroys superpositions of pure states as a consequence of entanglement with the environment. But decoherence can also be understood as “information leakage”, i.e., when knowledge of an encoded code block is transferred to the environment. In this event, the block’s information or entanglement content is typically lost.In a typical scenario, however, not all types of destructive events are likely to occur, but only those allowed by the information carrier, the type of interaction with the environment, and how the environment “picks up” information of the error events. These characteristics can be incorporated into a code, i.e., a channel-adapted quantum error-correcting code.Often, it is assumed that the environment’s ability to distinguish between error events is small, and I will denote such environments “memory-less”. But this assumption is not always valid, since the ability to distinguish error events is related to the temperature of the environment, and in the particular case of information coded onto photons, kBTR «ℏω typically holds, and one must then assume that the environment has a “memory”. In the thesis I describe a short quantum error-correction code adapted for photons interacting with a “cold” reservoir, i.e., a reservoir which continuously probes what error occurred in the coded state.I also study other types of environments, and show how to distill meaningful figures of merit from codes adapted for these channels, as it turns out that resource-based figures reflecting both information and entanglement can be calculated exactly for a well-studied class of channels: the Pauli channels. Starting from these resource-based figures, I establish the notion of efficiency and quality and show that there will be a trade-off between efficiency and quality for short codes. Finally I show how to incorporate, into these calculations, the choices one has to make when handling quantum states that have been detected as incorrect, but where no prospect of correcting them exists, i.e., so-called detection errors.
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