Repeater Insertion Research Articles

Analytical Analysis of Power-Constrained Repeaters’ Insertion in Large-Scale CMOS Chips

As the die area of CMOS integrated circuits continues to increase, interconnects will become dominant in determining the performance of the circuits from the standpoint of speed and power consumption. Uniform repeater insertion is an effective method used to reduce the propagation delay of a signal in long resistive-capacitive lines. However, non-optimal repeaters’ insertion yields non-optimal circuit performance. In this work, we provide a mathematical treatment for optimal repeater insertion with power consumption constraints. In particular, a closed-form expression for the optimum number and size of repeaters is given for a two-stage buffer used as a repeater. The validation of the analytical solution is assessed by means of circuit simulations, by comparing the theoretical optimal number and size of the repeaters to be placed in the long resistive-capacitive line with the simulated values.

Actively Expressed Intergenic Genes Generated by Transposable Element Insertions in Gossypium hirsutum Cotton.

The genomes and annotated genes of allotetraploid cotton Gossypium hirsutum have been extensively studied in recent years. However, the expression, regulation, and evolution of intergenic genes (ITGs) have not been completely deciphered. In this study, we identified a novel set of actively expressed ITGs in G. hirsutum cotton, through transcriptome profiling based on deep sequencing data, as well as chromatin immunoprecipitation, followed by sequencing (ChIP-seq) of histone modifications and how the ITGs evolved. Totals of 17,567 and 8249 ITGs were identified in G. hirsutum and Gossypium arboreum, respectively. The expression of ITGs in G. hirsutum was significantly higher than that in G. arboreum. Moreover, longer exons were observed in G. hirsutum ITGs. Notably, 42.3% of the ITGs from G. hirsutum were generated by the long terminal repeat (LTR) insertions, while their proportion in genic genes was 19.9%. The H3K27ac and H3K4me3 modification proportions and intensities of ITGs were equivalent to genic genes. The H3K4me1 modifications were lower in ITGs. Additionally, evolution analyses revealed that the ITGs from G. hirsutum were mainly produced around 6.6 and 1.6 million years ago (Mya), later than the pegged time for genic genes, which is 7.0 Mya. The characterization of ITGs helps to elucidate the evolution of cotton genomes and shed more light on their biological functions in the transcriptional regulation of eukaryotic genes, along with the roles of histone modifications in speciation and diversification.

Endoscopic Ultrasound-guided Transmural Biliary Drainage With 6 mm and 8mm Cautery-enhanced Lumen-apposing Metal Stents: A Multicenter Collaborative Study.

Endoscopic retrograde cholangiopancreatography (ERCP) may be unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative. We aimed to assess the efficacy and safety of EUS-BD for malignant distal bile duct obstruction using the newly introduced smaller caliber 6 or 8 mm cautery-enhanced lumen-apposing metal stent. A multicenter retrospective study was performed on patients with unresectable malignant distal bile duct obstruction who underwent EUS-BD between 2021 and 2022 after unsuccessful ERCP. Thirty-two patients were included [7 (53.13%) males], with a mean age of 72.2 ± 12.5 years. The technical success rate was 100%. Altered anatomy was present in 2 (6.25%). The indication for drainage was biliary obstruction from pancreatic cancer in 26 patients (84.5%), cholangiocarcinoma in 3 (9.4%), and ampullary mass in 3 (9.4%). The procedure was performed mostly in an outpatient setting (n = 19, 59.38%). The clinical success rate was 92.3% [bilirubin: 14.1 (SD: 8.9) preprocedure vs 4.9 (SD: 1.1) postprocedure; P = 0.0001]. There was one early adverse event of a perforation, which was closed endoscopically and drained percutaneously. Delayed adverse events included food impaction of the stent (n = 1), which was resolved with a repeat procedure and insertion of a double pigtail stent. This study demonstrates the feasibility of EUS-BD drainage using smaller caliber 6 or 8 mm lumen-apposing metal stent to relieve malignant distal bile duct obstruction in patients who fail conventional ERCP.

Emergence of a novel GIII Getah virus variant in pigs in Guangdong, China, 2023.

From May to July of 2023, one pig farm in Heyuan city, Guangdong Province of China, suffered severe piglet death and sow reproductive disorders. The common pig viruses and bacteria tested negative. To uncover the possible cause of the disease, a metagenomic analysis was performed in the pooled small intestine samples from three 8-day-old diseased piglets. The results showed that Getah virus (GETV), an RNA virus, might be the potential pathogen that affects pig health. Subsequently, GETV nucleotide was detected in all of the 15 samples collected from three diseased piglets using quantitative reverse transcription PCR, suggesting GETV as the main pathogen of the disease. A GETV strain, designated as GDHYLC23, was successfully isolated using the swine testicle cell line. Sequence analysis showed that the epidemic strain had a unique 32-nucleotide repeat insertion in the 3' noncoding region. Phylogenetic analysis showed that GDHYLC23 belonged to the pandemic group III. The identification of GETV with new variations implies the continuous evolution of the virus, which poses potential threats to the swine industry.IMPORTANCEPig farms are faced with emerging and re-emerging viruses that may cause substantial economic loss. The identification of potentially pathogenic viruses helps to prevent and control the spread of diseases. In this study, by using metagenomic analysis, we found that a neglected virus, GETV with a unique insertion in the genome, was the main pathogen in one pig farm that suffered severe piglet death and sow reproductive disorders. Although the potential impact of such an insertion on viral pathogenicity is unknown, the surveillance of the continuing evolution of GETV in pig farms cannot be ignored.

Efficient fabrication of high-quality graphene via alternating-current co-intercalation and microwave-assisted expansion

To facilitate the transformation of inexpensive and abundant graphite resources into two-dimensional graphene materials with promising applications, the development of efficient, cost-effective, and scalable technologies for large-scale production of high-quality graphene is crucial. Here, we propose an effective electrochemical dual-electrode co-intercalation exfoliation strategy. During the process, precise control of the electrochemical intercalation is achieved by adjusting the working bias and alternating current (AC) cycle, while ensuring the ion insertion rate through gradual voltage escalation. Repeated insertion of cations and anions under AC accelerates the graphite exfoliation. Following complete ion inserting, suitable microwave processing was employed to achieve rapid graphite expansion. Ultimately, ultra-sonication in NMP is employed to achieve final exfoliation between graphite layers. The resulting few-layer graphene (2–3 layers) exhibited minimal defects (ID/IG = 0.0405), low oxygen content (C/O = 44.62), high yield (95.3 %), and excellent conductivity (625 S/cm), enabling its potential commercialization and large-scale application. This outcome also serves as a significant reference for the commercial production of environmentally friendly and cost-effective graphene.

Chromosome-scale genome assembly clarifies the mechanism of flooding tolerance and evolutionary history of Myricaria laxiflora

Myricaria laxiflora, belonging to the Tamaricaceae family, is a valuable plant resource naturally occurring along the riverbanks of the Yangtze River Basin. In this study, we constructed a chromosome-level M. laxiflora genome which was 1.34 Gb in size, with 12 chromosomes and a contig N50 of 11.69 Mb. In total, 23,719 protein-coding genes were discovered across the M. laxiflora genome. Phylogenetic investigation indicated that Tamaricaceae and Polygonaceae diverged between 65 and 81 million years ago (Mya). M. laxiflora underwent one whole genome duplication (WGD) between 19.74 and 24.60 Mya, and experienced a long terminal repeat (LTR) insertion around 0.15 Mya. These genomic changes may be related to environmental upheavals (such as the uplift of the Qinghai-Tibet Plateau) experienced by M. laxiflora during its evolution, and also may have provided a foundation for its evolution and adaptation. To analyze the flooding adaption mechanism of M. laxiflora, we compared morphological, physiological, and transcriptomic changes under control and submerged conditions. Overall, M. laxiflora was found to adopt a "quiescence" strategy when completely submerged. Specifically, in response to submersion, photosynthesis weakens, growth stagnates, glycolysis is activated, and the antioxidant enzyme system is enhanced. The “ethylene response pathway” was ascertained as a likely regulator of this process, and a MlERF-VII gene (Mla11G026380) may be the key gene regulating this process. Our findings shed light on the underlying mechanisms behind the flooding resistance displayed by M. laxiflora, while also establishing a basis for the conservation of its genetic resources.

Identification of transcription factors contributing to vitamin C synthesis during Rosa roxburghii fruit development by integrating transcriptomics and metabolomics

Ascorbic acid, also referred to as vitamin C (Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains very high levels of Vc. However, the Vc content of R. roxburghii varies considerably during plant development and ripening. To better understand the molecular mechanisms that underlie fluctuations in Vc content of R. roxburghii fruit at different developmental stages, we performed transcriptomic and metabolomic analyses and identified two significant gene networks/modules and 168 transcription factors directly involved in Vc synthesis. Promoter analysis of two core genes involved in Vc synthesis, RrGGP and RrGalUR, revealed the presence of a retroviral long terminal repeat (LTR) insert in the RrGalUR promoter. Using yeast one-hybrid and dual-luciferase assays, we demonstrated that the transcription factors RrHY5H and RrZIP9 bind to the promoter of RrGGP to promote its expression. RrZIP6 and RrWRKY4 bind to the LTR in the RrGalUR promoter to promote its expression. Our results reveal a molecular mechanism that controls Vc synthesis and accumulation in R. roxburghii fruit.

The 3′ UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S.aureus isolates. The regulatory 3' UTR of the vigR mRNA contributes to vancomycin tolerance and upregulates the autolysin IsaA. Using MS2-affinity purification coupled with RNA sequencing, we find that the vigR 3' UTR also regulates dapE, a succinyl-diaminopimelate desuccinylase required for lysine and peptidoglycan synthesis, suggesting a broader role in controlling cell wall metabolism and vancomycin tolerance. Deletion of the 3' UTR increased virulence, while the isaA mutant is completely attenuated in a wax moth larvae model. Sequence and structural analyses of vigR indicated that the 3' UTR has expanded through the acquisition of Staphylococcus aureus repeat insertions that contribute sequence for the isaA interaction seed and may functionalize the 3' UTR.

Novel genotype–phenotype correlations, differential cerebellar allele-specific methylation, and a common origin of the (ATTTC)n insertion in spinocerebellar ataxia type 37

Spinocerebellar ataxia subtype 37 (SCA37) is a rare disease originally identified in ataxia patients from the Iberian Peninsula with a pure cerebellar syndrome. SCA37 patients carry a pathogenic intronic (ATTTC)n repeat insertion flanked by two polymorphic (ATTTT)n repeats in the Disabled-1 (DAB1) gene leading to cerebellar dysregulation. Herein, we determine the precise configuration of the pathogenic 5ʹ(ATTTT)n–(ATTTC)n–3ʹ(ATTTT)n SCA37 alleles by CRISPR–Cas9 and long-read nanopore sequencing, reveal their epigenomic signatures in SCA37 lymphocytes, fibroblasts, and cerebellar samples, and establish new molecular and clinical correlations. The 5ʹ(ATTTT)n–(ATTTC)n–3ʹ(ATTTT)n pathogenic allele configurations revealed repeat instability and differential methylation signatures. Disease age of onset negatively correlated with the (ATTTC)n, and positively correlated with the 3ʹ(ATTTT)n. Geographic origin and gender significantly correlated with age of onset. Furthermore, significant predictive regression models were obtained by machine learning for age of onset and disease evolution by considering gender, the (ATTTC)n, the 3ʹ(ATTTT)n, and seven CpG positions differentially methylated in SCA37 cerebellum. A common 964-kb genomic region spanning the (ATTTC)n insertion was identified in all SCA37 patients analysed from Portugal and Spain, evidencing a common origin of the SCA37 mutation in the Iberian Peninsula originating 859 years ago (95% CI 647–1378). In conclusion, we demonstrate an accurate determination of the size and configuration of the regulatory 5ʹ(ATTTT)n–(ATTTC)n–3ʹ(ATTTT)n repeat tract, avoiding PCR bias amplification using CRISPR/Cas9-enrichment and nanopore long-read sequencing, resulting relevant for accurate genetic diagnosis of SCA37. Moreover, we determine novel significant genotype–phenotype correlations in SCA37 and identify differential cerebellar allele-specific methylation signatures that may underlie DAB1 pathogenic dysregulation.

ATR blocks telomerase from converting DNA breaks into telomeres.

Telomerase, the enzyme that maintains telomeres at natural chromosome ends, should be repressed at double-strand breaks (DSBs), where neotelomere formation can cause terminal truncations. We developed an assay to detect neotelomere formation at Cas9- or I-SceI-induced DSBs in human cells. Telomerase added telomeric repeats to DSBs, leading to interstitial telomeric repeat insertions or the formation of functional neotelomeres accompanied by terminal deletions. The threat that telomerase poses to genome integrity was minimized by ataxia telangiectasia and Rad3-related (ATR) kinase signaling, which inhibited telomerase at resected DSBs. In addition to acting at resected DSBs, telomerase used the extruded strand in the Cas9 enzyme-product complex as a primer for neotelomere formation. We propose that although neotelomere formation is detrimental in normal human cells, it may allow cancer cells to escape from breakage-fusion-bridge cycles.

On the interdependence of insertion forces, insertion speed, and lubrication: Aspects to consider when testing cochlear implant electrodes.

During the insertion of cochlear implant (CI) electrode arrays, forces occur which may cause trauma and poorer hearing outcomes. Unfortunately, research groups investigating factors influencing insertion forces come to contradicting results, especially regarding insertion speed. This study was conducted to investigate the origin of these contradicting results and to determine how different testing conditions influence experimental findings. Repeated, automated insertions with three different FLEX28 CI electrode arrays (MED-EL, Innsbruck, Austria) were performed into a newly developed, anatomically correct and 3D-printed mean scala tympani phantom. The testing protocol for each electrode included variations in insertion speed (v = 0.1-2.0 mm/s) and lubrication (90%, 50%, and 10% liquid soap), resulting in 51 insertions per electrode array and a total of 153 insertions. The test setup and protocol allowed for repeatable insertions with only minimal change in the morphology of the insertion force profiles per testing condition. Strong but varying dependencies of the maximal insertion forces and work were found regarding both lubrication and speed: work-speed dependency is constant for the 10% lubricant, negative for the 50% lubricant and positive for the 90% lubricant. Our results can explain part of the contradicting results found within previous studies by translating interrelations known from lubricated rubber friction to the field of CI electrode array insertion. We show that the main driver behind measured bulk forces are most likely the generated friction forces, which are strongly dependent on insertion speed and lubrication. The employed test setup allows for conducting repeatable and comparable insertion studies, which can be recapitulated by other centers due to the detailed explanation of the test setup as well as the developed and freely available insertion phantom. This study hence represents another important step toward standardizing CI array insertion testing.

Pentanucleotide Repeat Insertions in RAI1 Cause Benign Adult Familial Myoclonic Epilepsy Type 8.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disorder characterized by cortical tremors and seizures. Six types of BAFME, all caused by pentanucleotide repeat expansions in different genes, have been reported. However, several other BAFME cases remain with no molecular diagnosis. We aim to characterize clinical features and identify the mutation causing BAFME in a large Malian family with 10 affected members. Long-read whole genome sequencing, repeat-primed polymerase chain reaction and RNA studies were performed. We identified TTTTA repeat expansions and TTTCA repeat insertions in intron 4 of the RAI1 gene that co-segregated with disease status in this family. TTTCA repeats were absent in 200 Malian controls. In the affected individuals, we found a read with only nine TTTCA repeat units and somatic instability. The RAI1 repeat expansions cause the only BAFME type in which the disease-causing repeats are in a gene associated with a monogenic disorder in the haploinsufficiency state (ie, Smith-Magenis syndrome [SMS]). Nevertheless, none of the Malian patients exhibited symptoms related to SMS. Moreover, leukocyte RNA levels of RAI1 in six Malian BAFME patients were no different from controls. These findings establish a new type of BAFME, BAFME8, in an African family and suggest that haploinsufficiency is unlikely to be the main pathomechanism of BAFME. © 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Genomic evolution and insights into agronomic trait innovations of Sesamum species

Sesame is an ancient oilseed crop with high oil content and quality. However, the evolutionary history and genetic mechanisms of its valuable agronomic traits remain unclear. Here, we report chromosome-scale genomes of cultivated sesame (Sesamum indicum L.) and six wild Sesamum species, representing all three karyotypes within this genus. Karyotyping and genome-based phylogenic analysis revealed the evolutionary route of Sesamum species from n = 13 to n = 16 and revealed that allotetraploidization occurred in the wild species Sesamum radiatum. Early divergence of the Sesamum genus (48.5–19.7 million years ago) during the Tertiary period and its ancient phylogenic position within eudicots were observed. Pan-genome analysis revealed 9164 core gene families in the 7 Sesamum species. These families are significantly enriched in various metabolic pathways, including fatty acid (FA) metabolism and FA biosynthesis. Structural variations in SiPT1 and SiDT1 within the phosphatidyl ethanolamine-binding protein gene family lead to the genomic evolution of plant-architecture and inflorescence-development phenotypes in Sesamum. A genome-wide association study (GWAS) of an interspecific population and genome comparisons revealed a long terminal repeat insertion and a sequence deletion in DIR genes of wild Sesamum angustifolium and cultivated sesame, respectively; both variations independently cause high susceptibility to Fusarium wilt disease. A GWAS of 560 sesame accessions combined with an overexpression study confirmed that the NAC1 and PPO genes play an important role in upregulating oil content of sesame. Our study provides high-quality genomic resources for cultivated and wild Sesamum species and insights that can improve molecular breeding strategies for sesame and other oilseed crops.

Pooled analysis of patients with inherited prion disease caused by two- to twelve-octapeptide repeat insertions in the prion protein gene (PRNP).

Inherited prion diseases caused by two- to twelve-octapeptide repeat insertions (OPRIs) in the prion protein gene (PRNP) show significant clinical heterogeneity. This study describes a family with two new cases with a 4-OPRI mutation and two asymptomatic mutation carriers. The pooled analysis summarizes all cases reported in the literature to date and describes the relation between survival, age of onset, number of OPRI and codon 129 polymorphism. MEDLINE and Google Scholar were queried from database inception up to December 31, 2022. Age of onset was compared per number of OPRI and per codon 129 polymorphism using the Kruskal-Wallis and Wilcoxon-Mann-Whitney tests, respectively. Disease duration was modeled non-parametrically by a Kaplan-Meier model and semi-parametrically by a Cox model. This study comprised 164 patients. Lower number of OPRI and presence of valine (cis-V) versus methionine (cis-M) on codon 129 were associated with an older age of onset (P < 0.001 and P = 0.025, respectively) and shorter disease duration (P < 0.001 and P = 0.003, respectively). Within patients with 5- or more OPRI codon cis-V remained significantly associated with a shorter disease duration. Codon 129 homozygosity versus heterozygosity was not significantly associated with age of onset or disease duration (P = 0.076 and P = 0.409, respectively). This study summarized the largest cohort of patients with two- to twelve-OPRI to date. Lower number of OPRI and codon 129 cis-V is associated with an older age of onset and shorter disease duration, while homozygosity or heterozygosity on codon 129 was not.

Four Octapeptide Repeat Insertion (4-OPRI) in PRNP Causing Huntington Disease Phenocopy.

Four Octapeptide Repeat Insertion (4-OPRI) in PRNP Causing Huntington Disease Phenocopy.

VarSCAT: A computational tool for sequence context annotations of genomic variants.

The sequence contexts of genomic variants play important roles in understanding biological significances of variants and potential sequencing related variant calling issues. However, methods for assessing the diverse sequence contexts of genomic variants such as tandem repeats and unambiguous annotations have been limited. Herein, we describe the Variant Sequence Context Annotation Tool (VarSCAT) for annotating the sequence contexts of genomic variants, including breakpoint ambiguities, flanking bases of variants, wildtype/mutated DNA sequences, variant nomenclatures, distances between adjacent variants, tandem repeat regions, and custom annotation with user customizable options. Our analyses demonstrate that VarSCAT is more versatile and customizable than the currently available methods or strategies for annotating variants in short tandem repeat (STR) regions or insertions and deletions (indels) with breakpoint ambiguity. Variant sequence context annotations of high-confidence human variant sets with VarSCAT revealed that more than 75% of all human individual germline and clinically relevant indels have breakpoint ambiguities. Moreover, we illustrate that more than 80% of human individual germline small variants in STR regions are indels and that the sizes of these indels correlated with STR motif sizes. VarSCAT is available from https://github.com/elolab/VarSCAT.

Dynamic object–fruit combinations by introduced Tanimbar corellas (Cacatua goffiniana) in Singapore

Abstract Tanimbar corellas, an important model in comparative cognition research, are endemic to the Tanimbar Islands, Indonesia, but were also introduced to several other locations with a tropical climate. Introduced psittacines offer valuable opportunities to test hypotheses at large temporal and spatial scales, such as geographic distribution of behaviours. Here, we report two opportunistic observations of Tanimbar corellas combining small wooden fragments with two types of tropical fruit (Ketapang and Pong-pong) in Singapore. The observations were recorded and uploaded to YouTube by a local bird-watcher. We analyse the behavioural similarities and differences between object combinations with the Pong-pong fruit in Singapore and extractive tool use on the Wawai fruit in Indonesia. Repeated insertions of the wooden fragment into the fruit and visible ingestion suggest that the combinatory behaviours were most likely related to foraging. This report provides first insights into the presence of advanced technical abilities in geographically separated Tanimbar corellas.

Genetic analysis of a child with SATB2‑associated syndrome and literature study.

The present study aimed to investigate clinical phenotype and genotype characteristics of a male child with SATB2-associated syndrome (SAS) and analyzed the relationship between these characteristics and the possible underlying genetic mechanism. His clinical phenotype was analyzed. Using a high-throughput sequencing platform, his DNA samples were subjected to medical exome sequencing, screened for suspected variant loci and analyzed for chromosomal copy number variations. The suspected pathogenic loci were verified by Sanger sequencing. He presented with phenotypic anomalies of delayed growth, delayed speech and mental development, facial dysmorphism showing the typical manifestation of SAS and motor retardation symptoms. Gene sequencing result analyses revealed a de novo heterozygous repeat insertion shift mutation in the SATB2 gene (NM_015265.3) c.771dupT (p.Met258Tyrfs*46), resulting in a frameshift mutation from methionine to tyrosine at the amino acid site 258 and a truncated protein with 46 amino acids missing. The parents showed no mutation at this locus. This mutation was identified as the nosogenesis of this syndrome in children. To the best of the authors' knowledge, this is the first report on this mutation. The clinical manifestations and gene variation characteristics of 39 previously reported SAS cases were analyzed together with this case. The findings of the present study suggested severely impaired language development, facial dysmorphism and varying degrees of delayed intellectual development as the characteristic clinical manifestations of SAS.

Genetic screening for Huntington disease phenocopies in Sweden: A tertiary center case series focused on short tandem repeat (STR) disorders

ObjectiveTo perform a screening for Huntington disease (HD) phenocopies in a Swedish cohort. MethodsSeventy-three DNA samples negative for HD were assessed at a tertiary center in Stockholm. The screening included analyses for C9orf72-frontotemporal dementia/amyotrophic lateral sclerosis (C9orf72-FTD/ALS), octapeptide repeat insertions (OPRIs) in PRNP associated with inherited prion diseases (IPD), Huntington's disease-like 2 (HDL2), spinocerebellar ataxia-2 (SCA2), spinocerebellar ataxia 3 (SCA3) and spinocerebellar ataxia-17 (SCA17). Targeted genetic analysis was carried out in two cases based on the salient phenotypic features. ResultsThe screening identified two patients with SCA17, one patient with IPD associated with 5-OPRI but none with nucleotide expansions in C9orf72 or for HDL2, SCA2 or SCA3. Furthermore, SGCE-myoclonic-dystonia 11 (SGCE-M-D) and benign hereditary chorea (BHC) was diagnosed in two sporadic cases. WES identified VUS in STUB1 in two patients with predominant cerebellar ataxia. ConclusionsOur results are in keeping with previous screenings and suggest that other genes yet to be discovered are involved in the etiology of HD phenocopies.

Most Expected Winner: An Interpretation of Winners over Uncertain Voter Preferences

It remains an open question how to determine the winner of an election when voter preferences are incomplete or uncertain. One option is to assume some probability space over the voting profile and select the Most Probable Winner (MPW) -- the candidate or candidates with the best chance of winning. In this paper, we propose an alternative winner interpretation, selecting the Most Expected Winner (MEW) according to the expected performance of the candidates. We separate the uncertainty in voter preferences into the generation step and the observation step, which gives rise to a unified voting profile combining both incomplete and probabilistic voting profiles. We use this framework to establish the theoretical hardness of MEW over incomplete voter preferences, and then identify a collection of tractable cases for a variety of voting profiles, including those based on the popular Repeated Insertion Model (RIM) and its special case, the Mallows model. We develop solvers customized for various voter preference types to quantify the candidate performance for the individual voters, and propose a pruning strategy that optimizes computation. The performance of the proposed solvers and pruning strategy is evaluated extensively on real and synthetic benchmarks, showing that our methods are practical.