Up and Down: Mining Multidimensional Sequential Patterns Using Hierarchies

International audienceData warehouses contain large volumes of time-variant data stored to help analysis. Despite the evolution of OLAP analysis tools and methods, it is still impossible for decision makers to find data mining tools taking the specificity of the data (e.g. multidimensionality, hierarchies, time-variant) into account. In this paper, we propose an original method to automatically extract sequential patterns taking hierar- chies into account. This method extracts patterns that describe the inner trends by displaying patterns that either go from precise knowledge to general knowledge or go from general knowledge to precise knowledge. For instance, one rule exhibited could be data contain first many sales of coke in Paris and lemonade in London for the same date, followed by a large number of sales of soft drinks in Europe, which is said to be divergent (as precise results like coke precede general ones like soft drinks). On the opposite, rules like data contain first many sales of soft drinks in Europe and chips in London for the same date, followed by a large number of sales of coke in Paris are said to be convergent. In this paper, we define the concepts related to this original method as well as the associated algorithms. The experiments which we carried out show the interest of our proposal

Circular RNA CpG island hypermethylation-associated silencing in human cancer

Noncoding RNAs (ncRNAs), such as microRNAs and long noncoding RNAs (lncRNAs), participate in cellular transformation. Work done in the last decade has also demonstrated that ncRNAs with growth-inhibitory functions can undergo promoter CpG island hypermethylation-associated silencing in tumorigenesis. Herein, we wondered whether circular RNAs (circRNAs), a type of RNA transcripts lacking 5′-3′ ends and forming closed loops that are gaining relevance in cancer biology, are also a target of epigenetic inactivation in tumors. To tackle this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in conjuction with circRNA expression microarrays. We have found that the loss of DNA methylation provokes a release of circRNA silencing. In particular, we have identified that promoter CpG island hypermethylation of the genes TUSC3 (tumor suppressor candidate 3), POMT1 (protein O-mannosyltransferase 1), ATRNL1 (attractin-like 1) and SAMD4A (sterile alpha motif domain containing 4A) is linked to the transcriptional downregulation of both linear mRNA and the hosted circRNA. Although some circRNAs regulate the linear transcript, we did not observe changes in TUSC3 mRNA levels upon TUSC3 circ104557 overexpression. Interestingly, we found circRNA-mediated regulation of target miRNAs and an in vivo growth inhibitory effect upon TUSC3 circ104557 transduction. Data mining for 5′-end CpG island methylation of TUSC3, ATRNL1, POMT1 and SAMD4A in cancer cell lines and primary tumors showed that the epigenetic defect was commonly observed among different tumor types in association with the diminished expression of the corresponding transcript. Our findings support a role for circRNA DNA methylation-associated loss in human cancer

Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.

BackgroundAnimal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution.ResultsWe estimated expression of 97,217 L. hesperus transcripts in venom glands relative to silk and cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs), many of which BLAST and GO term analyses indicate may function as toxins or their delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of VSTs had predicted protein domains. Latrotoxins are venom toxins that cause massive neurotransmitter release from vertebrate or invertebrate neurons. We discovered ≥ 20 divergent latrotoxin paralogs expressed in L. hesperus venom glands, significantly increasing this biomedically important family. Mass spectrometry of L. hesperus venom identified 49 proteins from VSTs, 24 of which BLAST to toxins. Phylogenetic analyses showed venom gland specific gene family expansions and shifts in tissue expression.ConclusionsQuantitative expression analyses comparing multiple tissues are necessary to identify venom gland specific transcripts. We present a black widow venom specific exome that uncovers a trove of diverse toxins and associated proteins, suggesting a dynamic evolutionary history. This justifies a reevaluation of the functional activities of black widow venom in light of its emerging complexity

Phenotypic convergence in genetically distinct lineages of a Rhinolophus species complex (Mammalia, Chiroptera)

Phenotypes of distantly related species may converge through adaptation to similar habitats and/or because they share biological constraints that limit the phenotypic variants produced. A common theme in bats is the sympatric occurrence of cryptic species that are convergent in morphology but divergent in echolocation frequency, suggesting that echolocation may facilitate niche partitioning, reducing competition. If so, allopatric populations freed from competition, could converge in both morphology and echolocation provided they occupy similar niches or share biological constraints. We investigated the evolutionary history of a widely distributed African horseshoe bat, Rhinolophus darlingi , in the context of phenotypic convergence. We used phylogenetic inference to identify and date lineage divergence together with phenotypic comparisons and ecological niche modelling to identify morphological and geographical correlates of those lineages. Our results indicate that R. darlingi is paraphyletic, the eastern and western parts of its distribution forming two distinct non-sister lineages that diverged ~9.7 Mya. We retain R. darlingi for the eastern lineage and argue that the western lineage, currently the sub-species R . d. damarensis , should be elevated to full species status. R. damarensis comprises two lineages that diverged ~5 Mya. Our findings concur with patterns of divergence of other co-distributed taxa which are associated with increased regional aridification between 7-5 Mya suggesting possible vicariant evolution. The morphology and echolocation calls of R. darlingi and R. damarensis are convergent despite occupying different biomes. This suggests that adaptation to similar habitats is not responsible for the convergence. Furthermore, R. darlingi forms part of a clade comprising species that are bigger and echolocate at lower frequencies than R. darlingi , suggesting that biological constraints are unlikely to have influenced the convergence. Instead, the striking similarity in morphology and sensory biology are probably the result of neutral evolutionary processes, resulting in the independent evolution of similar phenotypes

06051 Abstracts Collection -- Kolmogorov Complexity and Applications

From 29.01.06 to 03.02.06, the Dagstuhl Seminar 06051 ``Kolmogorov Complexity and Applications\u27\u27 was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

Scrutinizing human MHC polymorphism:supertype analysis using Poisson-Boltzmann electrostatics and clustering

Peptide-binding MHC proteins are thought the most variable proteins across the human population; the extreme MHC polymorphism observed is functionally important and results from constrained divergent evolution. MHCs have vital functions in immunology and homeostasis: cell surface MHC class I molecules report cell status to CD8+ T cells, NKT cells and NK cells, thus playing key roles in pathogen defence, as well as mediating smell recognition, mate choice, Adverse Drug Reactions, and transplantation rejection. MHC peptide specificity falls into several supertypes exhibiting commonality of binding. It seems likely that other supertypes exist relevant to other functions. Since comprehensive experimental characterization is intractable, structure-based bioinformatics is the only viable solution. We modelled functional MHC proteins by homology and used calculated Poisson-Boltzmann electrostatics projected from the top surface of the MHC as multi-dimensional descriptors, analysing them using state-of-the-art dimensionality reduction techniques and clustering algorithms. We were able to recover the 3 MHC loci as separate clusters and identify clear sub-groups within them, vindicating unequivocally our choice of both data representation and clustering strategy. We expect this approach to make a profound contribution to the study of MHC polymorphism and its functional consequences, and, by extension, other burgeoning structural systems, such as GPCRs

척추동물아문 내 다른 계통 간 대진화를 이해하기 위한 생물정보학적 접근

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 협동과정 생물정보학전공, 2022. 8. 김희발.생물정보학은 디지털화된 유전서열정보를 토대로 다양한 생명현상의 원리를 규명하고 이를 활용해 인류의 삶의 질을 향상하는 것을 목적으로 할 것이다. 생물정보학적 연구는 각 종을 대표하는 표준유전체 구축으로 일반적으로 시작되고 미소 혹은 대진화에 대한 후속 연구를 진행한다. 비록 짧은 단편 해독 기술이 유전체 시대를 열었지만, 짧은 단편의 조립은 낮은 연결성이나 오류가 포함된 유전자 주석 등의 심각한 문제들을 가진다. 긴 단편 해독 기술은 염색체 수준의 주석 (scaffolds)에 필수적인 보다 긴 컨티그 (contig) 조립을 생산할 수 있다. 짧은 단편에서 긴 단편으로 변화하는 페러다임에 발 맞추어, 본 논문은 표준유전체 구축에서 비교유전체 분석까지 이어지는 일련의 생물정보학적 분석에 대한 집약적 연구를 수행했으며, 이는 다양한 척추동물 종들의 대진화를 이해하는 것이 목적이다. 제 1장에서는 연구의 일반적인 배경지식을 정리하였다. 첫째로, 염색체 수준의 주석을 달성한 표준유전체 구축의 페러다임 변화를 설명했다. 다음으로, 특이적 형질에 관련된 분자 진화를 규명하는 비교유전체 분석 방법 및 사례를 정리했다. 제 2장에서는 표준유전체를 구축한 사례로서, 대한민국의 고유종인 큰볏말뚝망둥어의 염색체 수준 표준유전체를 구축했다. 척추동물 유전체 프로젝트와 국제 협력을 통해 4가지 최신 유전체 해독기술들 (Pacbio CLR, 10X Genomics linked reads, Bionano optical mapping, 그리고 Arima Genomics Hi-C)을 활용하여, 기존 표준유전체와 비교해 연결성 (continuity, Scaffold N50 기준)이 약 100배 향상되고 총 25개의 염색체를 가진 고품질 표준유전체를 완성했다. 또한, Pacbio Isoseq전사체 데이터를 유전자 주석에 활용하여 총 24,744개의 유전자를 발굴했다. 제 3장에서는 표준유전체 품질 평가 방법과 비교유전체학적 분석을 접목한 사례로서, 분화 시기가 오래된 종 간에도 BUSCO 유전자를 활용해 염색체 수준의 진화 양상을 탐색하는 방법과 척추동물 내에서 사례를 제시했다. 또한, 포유류, 조류, 어류 등 다양한 척추동물의 표준유전체에서 후속 분석 상의 문제를 야기하는 허위 소실 및 중복 오류를 탐색하는 방법과 사례를 제시하고 발생원인을 밝혔다. 제 4장에서는 기존의 비교유전체학적 분석을 적용한 사례로서, 실러캔스를 포함하는 육기아강 단계통 파생적 진화에 대한 분석을 통해 육상 적응 및 사지 출현의 분자 기작을 규명했다. 제 5장에서는 새로운 비교유전체학적 분석을 적용한 사례로서, 발성학습 조류 및 대조군 각각의 다계통 수렴 진화에 대한 분석을 통해 아미노산 수렴의 진화적 법칙을 제안하고 발성 학습에 연관된 후보 유전자를 발굴했다. 이러한 표준유전체 구축에서부터 비교유전체 분석으로 이어지는 생물정보학적 접근을 통해 규명된 주요 연구결과 중에, 염색체 상 텔로미어 서열 분포 및 아미노산 수렴 진화의 원리는 척추동물 외에 다른 분류 군에서도 비교될 기준이 될 수 있을 것으로 기대된다. 또한, 사지 발달 및 발성 학습에 연관된 후보 유전자를 발굴한 비교유전체학적 접근법은 전 세계 다양한 생물들의 다양한 유용 형질에 연관된 유용 유전자를 발굴하는데 활용될 수 있을 것이다.Bioinformatics aims to improve the quality of life of mankind by decoding molecular mechanisms of biological phenomena based on digitalized sequence information of various species. It generally begins with a construction of reference genomes representing each species and moves on downstream analyses for microevolution within species and macroevolutions between species. Although short-read sequencing technologies initiated genomics era, the short read assemblies had critical problems for lower continuity and erroneous gene annotations causing mis-interpretations. Long read sequencing technologies improved assembly continuities fundamental to chromosome-level scaffolds and corrected false annotations. Following up the paradigm shift from short-reads to long-reads, here, I performed a series of bioinformatic analyses to understand macroevolutions of various vertebrate species from reference genome construction to comparative genome approaches. Chapter 1 summarized the general background of this dissertation. First, it described the paradigm shift of the reference genome constructions achieving chromosome-scale scaffolds. Next, comparative genomic approaches for specific traits were summarized. Chapter 2, as a case of constructing a reference genome, illuminated a chromosome-level reference genome of giant-fin mudskipper, an endemic species in republic of Korea. Based on the four latest genome sequencing technologies (Pacbio CLR, 10X Genomics linked reads, Bionano optical mapping, and Arima Genomics Hi-C) in the international cooperation with the Vertebrate genomes project, it improved the 100-fold longer continuity (Scaffold N50) with a total of 25 chromosomal-level scaffolds compared to that of the previous genome. In addition, a total of 24,744 genes were annotated with Pacbio Isoseq transcriptome data. In Chapter 3, as a case of combining the reference genome quality evaluation method and comparative genomic analyses, a method was developed to explore the chromosomal evolution between vertebrate species in distant lineages focusing on the BUSCO genes. In addition, it suggested methods for detecting false loss and duplication errors that cause problems in downstream analyses in reference genomes of various vertebrate lineages, such as, mammals, birds, and fishes, and revealed how those kinds of errors occurred. In Chapter 4, as a case using the existing comparative genomic approaches, the molecular mechanisms of terrestrial adaptation and limb emergence were identified by applying the series of analyses for apormorphic evolution of the monophyletic lineage of lobed-fin fishes including coelacanths and human. In Chapter 5, as a case developing a new comparative genomic approach, the rule of amino acid convergence was proposed and candidate genes related to vocal learning were discovered through the multi-omic analyses for convergent evolution between polyphyletic lineages of vocal learning bird and control groups. Among the major findings of this study based on the bioinformatics approaches from the reference genome construction to comparative genomic researches, telomere sequence distributions on chromosomes and the principles of amino acid convergence would be a standard for comparisons in various lineages. In addition, the systemized comparative genomic approaches that identified candidate genes involved in limb development and vocal learning may be utilized to discover new candidate genes associated with various useful traits of living things in the world.Chapter 1. LITERATURE REVIEW 1 1.1 Paradigm shift in reference genome constructions 2 1.2 Comparative genomics for specific traits 3 Chapter 2. CHROMOSOME-LEVEL GENOME ASSEMBLY OF PERIOPHTHALMUS MAGNUSPINNATUS: AN INDIGENOUS MUDSKIPPER IN THE YELLOW SEA 5 2.1 Abstract 6 2.2 Introduction 7 2.3 Materials and Methods 9 2.4 Results and Discussion 13 Chapter 3. COMPARATIVE GENOMIC APPROACHES TO DETECT ERRONEOUS GENES IN REFERENCE GENOMES AND TO VISUALIZE CHROMOSOME EVOLUTION ACROSS VERTEBRATES 24 3.1 Abstract 25 3.2 Introduction 26 3.3 Materials and Methods 28 3.4 Results and Discussion 32 Chapter 4. COELACANTH-SPECIFIC ADAPTIVE GENES GIVE INSIGHTS INTO PRIMITIVE EVOLUTION FOR WATER-TO-LAND TRANSITION OF TETRAPODS 59 4.1 Abstract 60 4.2 Introduction 61 4.3 Materials and Methods 63 4.4 Results 69 4.5 Discussion 79 Chapter 5. AMINO ACID CONVERGENCES BETWEEN INDEPENDENT LINEAGES IN BIRDS GIVE EVOLUTIONARY INSIGHTS INTO AVIAN VOCAL LEARNING 85 5.1 Abstract 86 5.2 Introduction 87 5.3 Materials and Methods 89 5.4 Results 98 5.5 Discussion 159 GENERAL DISCUSSUSION 167 REFERENCES 168 요약(국문초록) 176박

Viral infection reveals hidden sharing of TCR CDR3 sequences between individuals

The T cell receptor is generated by a process of random and imprecise somatic recombination. The number of possible T cell receptors which this process can produce is enormous, greatly exceeding the number of T cells in an individual. Thus, the likelihood of identical TCRs being observed in multiple individuals (public TCRs) might be expected to be very low. Nevertheless such public TCRs have often been reported. In this study we explore the extent of TCR publicity in the context of acute resolving Lymphocytic choriomeningitis virus (LCMV) infection in mice. We show that the repertoire of effector T cells following LCMV infection contains a population of highly shared TCR sequences. This subset of TCRs has a distribution of naive precursor frequencies, generation probabilities, and physico-chemical CDR3 properties which lie between those of classic public TCRs, which are observed in uninfected repertoires, and the dominant private TCR repertoire. We have named this set of sequences "hidden public" TCRs, since they are only revealed following infection. A similar repertoire of hidden public TCRs can be observed in humans after a first exposure to SARS-COV-2. The presence of hidden public TCRs which rapidly expand following viral infection may therefore be a general feature of adaptive immunity, identifying an additional level of inter-individual sharing in the TCR repertoire which may form an important component of the effector and memory response