Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

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Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases

Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2–33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7–5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals’ capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.publishedVersio

Transcriptome and genome sequencing uncovers functional variation in humans

Summary Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project – the first uniformly processed RNA-seq data from multiple human populations with high-quality genome sequences. We discovered extremely widespread genetic variation affecting regulation of the majority of genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on cellular mechanisms of regulatory and loss-of-function variation, and allowed us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Quantum error correction

This thesis intends to familiarise the reader with quantum error correction, and also show some relations to the well known concept of information - and the lesser known quantum information. Quantum information describes how information can be carried by quantum states, and how interaction with other systems give rise to a full set of quantum phenomena, many of which have no correspondence in classical information theory. These phenomena include decoherence, as a consequence of entanglement. Decoherence can also be understood as "information leakage", i.e., knowledge of an event is transferred to the reservoir - an effect that in general destroys superpositions of pure states. It is possible to protect quantum states (e.g., qubits) from interaction with the environment - but not by amplification or duplication, due to the "no-cloning" theorem. Instead, this is done using coding, non-demolition measurements, and recovery operations. 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".  This assumption is not always valid, since the ability to distinguish error events is related to the \emph{temperature} of the environment, and in the particular case of information coded onto photons,  typically holds, and one must then assume that the environment has a "memory". In this thesis, I describe a short quantum error-correcting code (QECC), adapted for photons interacting with a cold environment, i.e., this code protects from an environment that continuously records which error occurred in the coded quantum state. Also, it is of interest to compare the performance of different QECCs - But which yardstick should one use? We compare two such figures of merit, namely the quantum mutual information and the quantum fidelity, and show that they can not, in general, be simultaneously maximised in an error correcting procedure. To show this, we have used a five-qubit perfect code, but assumed a channel that only cause bit-flip errors. It appears that quantum mutual information is the better suited yardstick of the two, however more tedious to calculate than quantum fidelity - which is more commonly used.Denna avhandling är en introduktion till kvantfelrättning, där jag undersöker släktskapet med teorin om klassisk information - men också det mindre välkända området kvantinformation. Kvantinformation beskriver hur information kan bäras av kvanttillstånd, och hur växelverkan med andra system ger upphov till åtskilliga typer av fel och effekter, varav många saknar motsvarighet i den klassiska informationsteorin. Bland dessa effekter återfinns dekoherens - en konsekvens av s.k. sammanflätning. Dekoherens kan också förstås som "informationsläckage", det vill säga att kunskap om en händelse överförs till omgivningen - en effekt som i allmänhet förstör superpositioner i rena kvanttillstånd.  Det är möjligt att med hjälp av kvantfelrättning skydda kvanttillstånd (t.ex. qubitar) från omgivningens påverkan, dock kan sådana tillstånd aldrig förstärkas eller dupliceras, p.g.a icke-kloningsteoremet. Tillstånden skyddas genom att införa redundans, varpå tillstånden interagerar med omgivningen. Felen identifieras m.h.a. icke-förstörande mätningar och återställs med unitära grindar och ancilla-tillstånd.Men i realiteten kommer inte alla tänkbara fel att inträffa, utan dessa begränsas av vilken informationsbärare som används, vilken interaktion som uppstår med omgivningen, samt hur omgivningen "fångar upp" information om felhändelserna. Med kunskap om sådan karakteristik kan man bygga koder, s.k. kanalanpassade kvantfelrättande koder. Vanligtvis antas att omgivningens förmåga att särskilja felhändelser är liten, och man kan då tala om en minneslös omgivning. Antagandet gäller inte alltid, då denna förmåga bestäms av reservoirens temperatur, och i det speciella fall då fotoner används som informationsbärare gäller typiskt , och vi måste anta att reservoiren faktiskt har ett "minne". I avhandlingen beskrivs en kort, kvantfelrättande kod som är anpassad för fotoner i växelverkan med en "kall" omgivning, d.v.s. denna kod skyddar mot en omgivning som kontinuerligt registrerar vilket fel som uppstått i det kodade tillståndet.  Det är också av stort intresse att kunna jämföra prestanda hos kvantfelrättande koder, utifrån någon slags "måttstock" - men vilken? Jag jämför två sådana mått, nämligen ömsesidig kvantinformation, samt kvantfidelitet, och visar att dessa i allmänhet inte kan maximeras samtidigt i en felrättningsprocedur. För att visa detta har en 5-qubitarskod använts i en tänkt kanal där bara bitflip-fel uppstår, och utrymme därför finns att detektera fel. Ömsesidig kvantinformation framstår som det bättre måttet, dock är detta mått betydligt mer arbetskrävande att beräkna, än kvantfidelitet - som är det mest förekommande måttet.QC 20121206</p

Quantum error correction

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.QC 20160115</p

Quantum error correction

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.QC 20160115</p

Twist Solid GMS560 v0.6.1 references fuseq_wes

The data included here are part of a collection of different types of reference data used in the bioinformatic analysis pipeline called Twist Solid GMS560. The pipeline is based on the Hydra-genetics framework and analyses NGS short read data from the GMS560 Twist panel which is used on solid cancer samples. The data in this specific item include general publicly available reference files used in the pipeline by the fusion calling program FuSeq_WES (https://github.com/nghiavtr/FuSeq_WES). Downloading data from here will ensure compatible and correct versions.</p