L’accumulation de remaniements de la structure des chromosomes aussi appelés variations structurelles (SV) est un important contributeur à la transformation des cellules malignes et à la constitution d’une hétérogénéité intratumorale. Nous avons développé un outil bio-informatique qui permet désormais d’obtenir une image fine de ces SV qui se produisent dans le génome humain. Nous avons ainsi pu démontrer l’existence de SV présentes à de faibles fréquences dans différentes populations cellulaires supposées clonales montrant que les taux de formation des SV pourraient être grandement sous-estimés. Parallèlement, nous avons montré que le niveau d’instabilité des individus dépend de facteurs génétiques de prédisposition. Pour les identifier, nous avons développé des systèmes génétiques de mesure des taux de SV chez la levure qui vont nous permettre d'identifier les gènes contrôlant l'instabilité chromosomique par analyse de liaison à grande échelle. Ces régulateurs représenteront de nouveaux gènes candidats impliqués dans le développement du cancer chez l’homme, car les déterminants génétiques impliqués dans le métabolisme de l'ADN sont très conservés entre la levure et les mammifères. / The accumulation of chromosomal rearrangements also called Structural Variations (SV) is a major contributor to the transformation of tumoral cells and to the constitution of intratumoral heterogeneity. We have developed a bio-informatic tool that can now provide a sharp image of SV that occur in the human genome. We have demonstrated the existence of SV present in low proportions in different supposedly clonal cell populations showing that the rates of SV formation could be greatly underestimated. In parallel, we have shown that the level of instability of the genome depends on predisposition factors. To identify those, we have developed genetic assays to measure the rate of SV in yeast that will allow us to identify new genes controlling the stability of the genome using large scale linkage analysis. These regulators represent new gene-candidates involved in the development of cancer in human as the determinants involved in DNA metabolism are very conserved between yeast and mammals.

Les variants structuraux génomiques (SVs) composent une large part du polymorphisme observable entre les individus mais leurs impacts sur les processus micro-évolutifs restent mal connus et leur étude à large échelle est rare.La première partie de ce manuscrit est une étude de la bibliographie portant sur les SVs décrits chez les animaux domestiques. Cette partie met en avant l'importance des SVs dans la modification des gènes ou de leur régulation, impactant un grand nombre de traits sélectionnés lors de la domestication, en lien avec la productivité, la morphologie ou encore le comportement.Basée sur l’étude de données de reséquençage de 500 génomes complets de petits ruminants sauvages et domestiques, la seconde partie, ciblant trois SVs décrits dans la bibliographie, a permis (i) de réfuter l’hypothèse d’amplification en lien avec la domestication des copies endogènes protectrices du retrovirus JSRV situées dans la région 6q13 du mouton, (ii) d’identifier des duplications entourant et affectant le gène ASIP qui seraient impliquées dans les modifications de coloration du pelage en lien avec la domestication des petits ruminants, ainsi que (iii) de montrer un potentiel rôle adaptatif d'un haplotype du locus de la beta-globine lié au climat aride chez le mouton.La troisième partie se base sur une recherche sans a priori de l’ensemble des SVs présents dans des génomes complets. Au travers du développement d’une méthode de détection des SVs et de son application, cette partie permet de décrire environ 50k et 20k SVs dans les génomes des Ovis et des Capra. Parmi ces SVs, 135 chez Ovis et 70 chez Capra semblent liés à la domestication et affectent des gènes impliqués dans l’amélioration, l’immunité, la reproduction ou la survie. De plus, les distributions de 130 SVs pour les moutons et 35 SVs pour les chèvres covarient avec des variables environnementales au Maroc. Certains affectent des gènes impliqués dans la morphologie, l’immunité et le métabolisme.Ce travail met ainsi en avant de nombreux variants qui peuvent impacter des gènes et qui ont pu être ciblés lors la domestication initiale, des étapes d’amélioration ultérieure ou de l’adaptation locale des petits ruminants. Il démontre l'importance de prendre en compte les variants structuraux dans les études génomiques visant à décrire les bases génétiques de la domestication. / Genomic structural variations (SVs) account for a large part of the polymorphism between individuals, but their impacts on micro-evolutionary processes remain poorly known and large-scale studies are scarce.The first part of this manuscript is a bibliographic study of SVs in domestic animals. This part highlights the importance of SVs in modifying genes or their regulation, impacting a large number of traits selected during domestication and linked to productivity, morphology or behaviour.Based on the study of resequenced data from 500 whole genomes of wild and domestic small ruminants, the second part, targeting three SVs described in the bibliography, allowed (i) to refute the hypothesis of a link between the domestication of sheep and the amplification of endogenous protective copies of the JSRV retrovirus located in the 6q13 region, l, (ii) to identify duplications surrounding and affecting the ASIP gene that could be involved in the coat color changes related to the domestication of small ruminants, as well as (iii) highlight a potential adaptive role to arid climate of an haplotype of beta-globin locus in sheep.In the third part, we conducted a whole genome survey of SVs . Through the development of a SVs detection method and its application, we could detect about 50k and 20k SVs in Ovis and Capra. Of these SVs, 135 and 70 in Ovis and Capra, respectively, appear to be linked with domestication and affect genes involved in improvement, immunity, reproduction or survival. In addition, in Morocco, the distributions of 130 SVs for sheep and 35 SVs for goats covariate with environmental variables. Some of them affect genes involved in morphology, immunity and metabolism.This work highlights that many variants impacting genes might have been targeted during initial domestication and subsequent improvement steps or during the local adaptation of sheep and goats. It demonstrates the importance of considering structural variants in genomic studies to describe the genetic basis of domestication.

Les cultivars de bananiers sont dérivés d'hybridations entre sous-espèces de Musa acuminata (génome A) et pour certains avec l'espèce M. balbisiana (génome B). Ces hybrides présentent une fertilité réduite, des méioses perturbées et de fortes distorsions de ségrégation. Ces caractéristiques attribuées à des réarrangements chromosomiques entre espèces et sous-espèces compliquent les analyses génétiques et les programmes d'amélioration variétale. Au cours de cette thèse, nous avons mis en place et testé de nouvelles approches, basées sur la récente disponibilité d'une séquence de référence du bananier et des technologies de séquençage haut-débit, pour caractériser ces différences de structures chromosomiques et comprendre leur impact sur les ségrégations chromosomiques. Ces approches ont nécessité l'amélioration de la séquence de référence du bananier. Pour cela, des outils ont été développés. Ils sont applicables à d'autres génomes et modulables en fonction des données disponibles. Le nombre de scaffolds a été divisé par 5 et 90% de la séquence est maintenant ancré aux chromosomes. Les scaffolds correspondant au génome mitochondrial ont été identifiés et le génome chloroplastique a été assemblé et annoté. Des données de re-séquençage de l'accession ‘Pahang' et de génotypage dense de sa descendance ont été utilisées pour explorer l'origine des distorsions de ségrégation impliquant les chromosomes 1 et 4. L'ensemble des données (profils de distorsion et de recombinaison, appariements à la méiose, re-séquençage), nous orientent vers l'hypothèse d'une translocation réciproque en orientation inversée, entre régions distales des chromosomes 1 et 4. Le test de nos outils de recherche de variations structurales pour comparer les génomes A et B du bananier, dont les différences de structure sont connues, montre que nos outils détectent directement les signatures de certaines variations structurales mais que pour d'autres il ne détecte que des signatures partielles. Ces dernières peuvent néanmoins être informatives en complément d'autres types d'informations provenant de cartographie génétique et d'analyses cytogénétiques. / Banana cultivars are derived from hybridization between Musa acuminata subspecies (A genome) and, for some of them, with the species M. balbisiana (B genome). These hybrids have reduced fertility, disturbed meiosis and strong segregation distortions. These characteristics attributed to chromosomal rearrangements between species and subspecies complicate genetic analyses and breeding programs. In this thesis, we have developed and tested new approaches based on the recent availability of a banana reference genome sequence and high-throughput sequencing technologies, to characterize these differences in chromosomal structures and understand their impact on chromosomal segregation. These approaches needed improvement of the banana reference genome sequence. New bioinformatics tools were developed for this purpose. They are applicable to other genomes and are flexible according to available data. The scaffolds number was divided by 5 and 90% of the assembly is now anchored to the chromosomes. Scaffolds corresponding to the mitochondrial genome were identified and the chloroplast genome was assembled and annotated. Re-sequencing data from the 'Pahang' accession and dense genotyping of its progeny were used to explore the origin of segregation distortion involving chromosomes 1 and 4. Distortion and recombination profiles, chromosomal pairing at meiosis and re-sequencing data direct us to the hypothesis of a reciprocal translocation in inverted orientation between distal portions of chromosomes 1 and 4. We tested our structural variation research tools to compare the A and B genomes of banana, for which structural differences are known. The results showed that our tools detected complete signatures of some structural changes but for others, they only detected partial signatures. The latter can still be informative in addition to other informations derived from genetic mapping and cytogenetic studies.

Le récent développement des méthodes de séquençage permet aujourd’hui d’identifier des variations structurales chez de nombreuses espèces. Chez le maïs, des milliers de grandes insertions et délétions (InDel) de quelques pb à plusieurs centaines de Kbp ont été découvertes entre le génome de référence B73 et de nombreux autres génomes reséquencés. Ces InDel peuvent changer la composition des gènes entre les individus et donc être impliquées dans la variation du phénotype, mais cet effet sur le phénotype reste mal connu. L’objectif de cette thèse était d'étudier la contribution des InDel à l'adaptation, aux variations phénotypiques et aux performances hybrides chez le maïs. Nous avons développé une puce de génotypage des InDel Affymetrix® Axiom® capable de génotyper 105 927 InDel de 35bp à 129,7Kbp. 79 969 de ces InDel ont leur séquences absentes du génome de référence B73 et ont été identifiées par l’assemblage 3 génomes (F2, C103, and PH207). Nous avons sélectionné 61 492 InDel polymorphiques pour génotyper 362 lignées de maïs représentant une large gamme de diversité pour étudier la contribution des InDel à la diversité génétique, l’adaptation et la variation des caractères. Nous avons également génotypé 1 million de SNP à partir de deux puces de génotypage et du génotypage par séquençage pour étudier la complémentarité entre les InDel et les SNP. Qu’ils soient calculés avec les InDel ou les SNP la structuration génétique et les valeurs d’apparentement entre les lignées sont très similaires, ce qui suggère que la plupart des InDel ont suivi la même trajectoire évolutive que les SNP. 51% des InDel ne sont pas en déséquilibre de liaison élevé (>0.8) avec aucun SNP proche donc l’effet de ces InDel n’est donc a priori pas capturé pas des SNP à cette densité. Parmi les 294 régions génomiques associées au phénotype (QTL), 13 nouveaux QTL ont été détectés grâce aux InDel par rapport aux SNP par une approche de génétique d’association (GA). Nous avons détecté un enrichissement en InDel sous sélection entre les lignées tropicales, cornées et dentées par rapport aux SNP, avec 56 sur 188 régions sous sélection détectées avec les InDel. Ces régions contiennent des gènes impliqués dans l’adaptation et/ou la tolérance aux stress. De plus, le plus grand nombre d’associations a été découvert pour la floraison, caractère adaptatif chez le maïs. Ces résultats suggèrent que les InDel sont plus souvent impliquées dans l’adaptation et la tolérance aux stress. Nous avons enfin testé l’effet des InDel sur les performances hybride en analysant un panel de 287 hybrides issus du croisement de 210 lignées tempérées du panel précédent. Nous avons décomposé la variance des performances hybrides en distinguant les effets de dominance et d’additivité pour la floraison femelle (FF), la hauteur (PH) et le rendement (GY). La plus forte part de dominance et d’interaction génotype-environnement a été observée pour le GY et la plus faible pour la FF. L’effet additif et de dominance de 51,844 InDel et 469 267 SNP a été testé pour 4 combinaisons d’environnements par une approche de GA. 78 et 133 QTL avec un effet additif et dominant respectivement ont été identifiés, dont 6 et 11 avec des InDel. 83% de ces QTL ont été identifiés dans une seule combinaison d’environnements. Un des QTL de rendement identifié avec des InDel est situé dans un large cluster d’InDel sur le chromosome 6 et colocalise avec un QTL déjà identifié avec des SNP avec un effet fort dans l’augmentation du rendement sous des températures élevées. L’ajout de l’effet de dominance en plus de l’effet additif permet d’augmenter la précision des prédictions génomiques jusqu’à 5,6% pour le rendement. Cependant, l’ajout du génotypage des InDel en plus de celui des SNP n’a pas permis d’améliorer les prédictions des phénotypes hybrides. / In the last decades, the rapid development of genome sequencing allowed to identify structural variations in many species. In maize, thousands of large insertions and deletions (InDels) from few bp to hundreds of Kbp were discovered by comparing the reference genome B73 and many other resequenced genomes. These InDel sequences can carry genes and therefore be involved in phenotypic variation by changing the gene composition between individuals, but their effect on phenotype was not well studied. The aim of this thesis was to study the contribution of InDels to adaptation, phenotypic variations and hybrid performances in maize. We developed an Affymetrix® Axiom® genotyping array that allowed to genotype 105,947 InDels sequences ranging from 35bp to 129,7Kbp of size. 79,969 out 105,947 sequences of these InDels were not present in B73 reference genome and have been discovered by assembling three genomes (F2, C103, and PH207). We selected 61,492 polymorphic InDels to genotype a 362 maize inbred lines panel representing a broad range of diversity to study the contribution of InDels to genetic diversity, adaptation and trait variation. We also assembled one million of SNPs from two genotyping arrays and genotyping by sequencing to study the complementarity between InDels and SNPs. Genetic structuration and relatedness between inbred lines displayed by SNPs or by InDels were highly similar suggesting that almost all indels and SNPs followed a similar evolutionary trajectory. 51% of InDels were not in high linkage disequilibrium (LD>0.8) with any nearby SNP suggesting that the effect of these InDels was not be well captured using this density of SNP. Thanks to InDels, we detected 13 new quantitative trait loci (QTLs) among 294 QTLs identified for 23 traits by a genome wide association studies (GWAS). Similarly, 56 out 188 regions under selection between tropical, dent and flint maize lines were identified by InDels leading to an enrichment of genomic regions under selection detected by InDels compared to SNPs. These InDels include genes involved in tolerance to biotic and abiotic stress and/or adaptive traits as flowering time. Accordingly, the highest number of associated InDels was found for flowering time. These results suggest that InDels were often involved in adaptation and stress tolerance. In order to study the effect of InDels on hybrid performances, we analyzed a panel of 287 hybrids derived from the crossing of 210 maize temperate inbred lines from the previous panel. We decomposed the variance of female flowering (FF), plant height (PH) and grain yield (GY) by distinguishing the additive and dominant genetic effects. We observed the highest dominance and genotype by environment effects for GY and the lowest for FF. We performed GWAS on this panel by testing additive and dominance effects of 51,844 InDels and 469,267 SNPs on these three traits in 4 different environment combinations. We identified 78 and 133 QTLs with an additive and dominance effect, respectively including 6 and 11 QTLs discovered only by InDels. 83% of all QTLs were found with only one environment combination. One QTL for GY detected with InDels was located in a large cluster of InDels on chromosome 6, previously identified to have a strong effect on GY in heat conditions. We finally used InDels and/or SNPs genotyping to predict hybrid performances. Whereas including a dominance effect in genomic prediction models increased by 1.5 to 5.6% predictive abilities (PA) for GY, including InDels genotyping did not increased PA.

We developed a pipeline to identify the copy number polymorphisms (CNPs) in the Northern Swedish population using whole genome sequencing (WGS) data. Two different methodologies were applied to discover CNPs in more than 1,000 individuals. We also studied the association between the identified CNPs with the expression level of 438 plasma proteins collected in the same population. The identified CNPs were summarized and filtered as a population copy number matrix for 1,021 individuals in 243,987 non-overlapping CNP loci. For the 872 individuals with both WGS and plasma protein biomarkers data, we conducted linear regression analyses with age and sex as covariance. From the analyses, we detected 382 CNP loci, clustered in 30 collapsed copy number variable regions (CNVRs) that were significantly associated with the levels of 17 plasma protein biomarkers (p < 4.68×10-10).

När geotekniska laborationsanalyser utförs undersöks ofta kolvprover från olika djup som får representera marken vid det djupet provet är taget. I ett homogent lerskikt kan denna punkt antas vara representativ. I en icke-homogen lerjord, till exempel i varvig lera, skulle denna punkt kunna infalla i en icke-representativ variation. För att ta reda på om dessa strukturella variationer påverkar en leras mekaniska egenskaper har i denna studie lerprover från olika platser i Stockholms län analyserats. Genom laborationsundersökningar har lerornas vattenkvot, konflytgräns och lerhalt bestämts och jämförts med varandra. Konflytgränsen definieras som vattenkvoten då en lera går från plastisk konsistens till flytande konsistens och bestäms i denna studie med fallkonmetoden (Axelsson & Mattsson, 2016). Vattenkvoten anger förhållandet mellan jordens fasta massa och vattnets massa och bestäms genom vägning och torkning i ugn (Larsson, 2008). Lerhalten i ett jordprov bestäms genom en hydrometeranalys som anger mängden lera i förhållande till övriga kornstorlekar i provet. Proverna som har studerats i denna studie var av varierande kvalitet med avseende på varvighet och både glaciala och post-glaciala leror har undersökts. Resultatet visar att det är svårt att studera skillnader mellan ljusa och mörka variationer i leror som inte har en tydlig varvighet och att stora variationer förekommer i de undersökta parametrarna för mörka såväl som ljusa skikt. / When geotechnical laboratorial analyzes are executed, piston samples from different earth depths are commonly used. These samples will represent the soil at the given depth. The point at which the sample is taken could be seen as representative in a homogenous layer of clay but in an inhomogeneous layer, such as a varved glacial clay, this point could occur in a variation that is not representative for the whole layer. To find out if these structural variations will affect a clays mechanical properties clays from the Stockholm region have been analyzed. The clays water content, liquid limit and clay content has been determined through laboratorial analyzes and then compared with each other. The liquid limit is defined as the water content when a clay is transitioning from plastic to liquid consistency and is determined by the fall-cone method (Axelsson & Mattsson, 2016). The water content is determined through drying in a drying oven and gives the relationship between the soil’s solid mass and the mass of the water (Larsson, 2008). The clay content in a soil sample is determined through hydrometer analysis and gives a value on the amount of clay in relationship to other fractions. The samples which have been studied were of different quality with respect to how distinguishable the varves were and both glacial and post-glacial clays have been analyzed. The result show that it is difficult to analyze differences between light and dark variations and varvs in clays which does not have distinct layering and that vast variations occur in all of the analyzed parameters for both dark and light variations.

This thesis reports transport in ultrathin single crystalline nanowires of gold (∼ 2nm). These nanowires were fabricated using an oriented attachment process whereby nanoparticles of appropriate dimensions join in a linear fashion to form long and stable wires. The main motivation was to study the role of electron-electron interactions on the transport mechanism in case of a metallic system, as one approaches dimensions closer to the Fermi wavelength. The study forms the first of its kind in a simple metallic system of this dimension. Indeed, several new features have been obtained in this regard: Chapter 4 reports a breakdown of Fermi liquid state in such a system opening up possibilities of exotic states constituted by a strongly correlated Tomonaga-Luttinger liquid. We report consistent scaling of current-voltage curves, characteristic of such a phase and even resonant tunneling in such structures. The study reports the first observation of a correlated electron liquid in a metal, which has been observed only in semiconductors and polymer wires till date. Chapter 5 discusses the possibility of tuning the transport mechanism in these wires via a controlled change in the growth process. We show that using appropriate growth mechanisms, we can have a localized ground state as well, where variable range hopping is the dominant transport mechanism. Possibility of structural transitions in ultrathin wires is a field that has garnered considerable interest due to simulations. We present a highly sensitive tool in the form of electrical noise and its higher order statistics that can act as a detector of structural transitions. This has been thoroughly studied in case of conventional shape memory systems in Chapter 6. Preliminary noise studies on the nanowires have been reported in Chapter 7.

Les rétrotransposons sont des éléments génétiques mobiles qui constituent presque la moitié de notre génome. Seule la sous-famille L1HS appartenant à la classe des Long Interspersed Element-1(LINE-1 ou L1) a gardé une capacité de mobilité autonome chez l’Homme. Leur mobilisation dans la lignée germinale, mais Aussi dans certains tissus somatiques, contribue à la diversité du génome humain ainsi qu’à certaines maladies comme le cancer. Ainsi, de nouvelles copies de L1 peuvent directement s'intégrer dans des séquences codantes ou régulatrices, et altérer leur fonction. De plus, les séquences L1 contiennent elles-mêmes plusieurs éléments cis-régulateurs et leur insertion à proximité ou dans un gène peut produire des altérations génétiques plus subtiles. Afin d'explorer l'ensemble de ces altérations à l'échelle du génome, nous avons développé un logiciel dédié à l’analyse des données de séquençage d'ARN qui permet d'identifier des transcrits chimériques ou antisens impliquant les L1 et d'annoter ces isoformes en fonction des différents événements d’épissage alternatif subits. Au cours de ce travail, il est apparu que la compréhension du lien entre polymorphisme des insertions et phénotype nécessite une vue complète des différentes copies L1HS présentes chez un individu donné. Afin de disposer d'un catalogue aussi complet que possible de ces polymorphismes identifiés dans des échantillons humains sains ou pathologiques et publiés dans des journaux scientifiques, nous avons développé euL1db, la base de données des insertions de rétrotransposon L1HS chez l’Homme. En conclusion, ce travail aidera à comprendre l’impact des L1 sur l’expression des gènes, à l'échelle du génome. / Retrotransposons are mobile genetics elements, which form almost half of our genome. Only the L1HS subfamily of the Long Interspersed Element-1 class (LINE-1 or L1) has retained the ability to jump autonomously in humans. Their mobilization in the germline – but also in some somatic tissues – contributes to human genetic diversity and to diseases, such as cancer. L1 reactivation can be directly mutagenic by disrupting genes or regulatory sequences. In addition, L1 sequences themselves contain many regulatory cis-elements. Thus, L1 insertions near a gene or within intronic sequences can also produce more subtle genic alterations. To explore L1-mediated genic alterations in a genome-wide manner, we have developed a dedicated RNA-seq analysis software able to identify L1 chimeric or antisense transcripts and to annotate these novel isoforms with their associated alternative splicing events. During the course of this work, it appeared that understanding the link between L1HS insertion polymorphisms and phenotype or disease requires a comprehensive view of the different L1HS copies present in a given individual or sample. To provide a comprehensive summary of L1HS insertion polymorphisms identified in healthy or pathological human samples and published in peer-reviewed journals, we developed euL1db, the European database of L1HS retrotransposon insertions in humans. This work will help understanding the overall impact of L1 insertions on gene expression, at a genome-wide scale.

An influence of variations in human genome is perceptible at a first glance on human itself to see differences between the individuals and entire populations. Also, behavior or probability of certain diseases are influenced in large way by differences at genome's level. This work presents methods for detecting variations in the human genome that were developed after an arose of the second-generation sequencing technologies. A new tool that combines read pair and split read methods, with information about a depth of coverage was also designed and implemented. The tool was tested on simulated and real data and compared with a reference outputs.

Achieving high computation efficiency, in terms of Cycles per Instruction (CPI), for high-performance computing kernels is an interesting and challenging research area. Dense Linear Algebra (DLA) computation is a representative high-performance computing ap- plication, which is used, for example, in LU and QR factorizations. Unfortunately, mod- ern off-the-shelf microprocessors fall significantly short of achieving theoretical lower bound in CPI for high performance computing applications. In this thesis, we perform an in-depth analysis of the available parallelisms and propose suitable algorithmic and architectural variation to significantly improve the computation efficiency. There are two standard approaches for improving the computation effficiency, first, to perform application-specific architecture customization and second, to do algorithmic tuning. In the same manner, we first perform a graph-based analysis of selected DLA kernels. From the various forms of parallelism, thus identified, we design a custom processing element for improving the CPI. The processing elements are used as building blocks for a commercially available Coarse-Grained Reconfigurable Architecture (CGRA). By per- forming detailed experiments on a synthesized CGRA implementation, we demonstrate that our proposed algorithmic and architectural variations are able to achieve lower CPI compared to off-the-shelf microprocessors. We also benchmark against state-of-the-art custom implementations to report higher energy-performance-area product. DLA computations are encountered in many engineering and scientific computing ap- plications ranging from Computational Fluid Dynamics (CFD) to Eigenvalue problem. Traditionally, these applications are written in highly tuned High Performance Comput- ing (HPC) software packages like Linear Algebra Package (LAPACK), and/or Scalable Linear Algebra Package (ScaLAPACK). The basic building block for these packages is Ba- sic Linear Algebra Subprograms (BLAS). Algorithms pertaining LAPACK/ScaLAPACK are written in-terms of BLAS to achieve high throughput. Despite extensive intellectual efforts in development and tuning of these packages, there still exists a scope for fur- ther tuning in this packages. In this thesis, we revisit most prominent and widely used compute bound algorithms like GMM for further exploitation of Instruction Level Parallelism (ILP). We further look into LU and QR factorizations for generalizations and exhibit higher ILP in these algorithms. We first accelerate sequential performance of the algorithms in BLAS and LAPACK and then focus on the parallel realization of these algorithms. Major contributions in the algorithmic tuning in this thesis are as follows: Algorithms: We present graph based analysis of General Matrix Multiplication (GMM) and discuss different types of parallelisms available in GMM We present analysis of Givens Rotation based QR factorization where we improve GR and derive Column-wise GR (CGR) that can annihilate multiple elements of a column of a matrix simultaneously. We show that the multiplications in CGR are lower than GR We generalize CGR further and derive Generalized GR (GGR) that can annihilate multiple elements of the columns of a matrix simultaneously. We show that the parallelism exhibited by GGR is much higher than GR and Householder Transform (HT) We extend generalizations to Square root Free GR (also knows as Fast Givens Rotation) and Square root and Division Free GR (SDFG) and derive Column-wise Fast Givens, and Column-wise SDFG . We also extend generalization for complex matrices and derive Complex Column-wise Givens Rotation Coarse-grained Recon gurable Architectures (CGRAs) have gained popularity in the last decade due to their power and area efficiency. Furthermore, CGRAs like REDEFINE also exhibit support for domain customizations. REDEFINE is an array of Tiles where each Tile consists of a Compute Element and a Router. The Routers are responsible for on-chip communication, while Compute Elements in the REDEFINE can be domain customized to accelerate the applications pertaining to the domain of interest. In this thesis, we consider REDEFINE base architecture as a starting point and we design Processing Element (PE) that can execute algorithms in BLAS and LAPACK efficiently. We perform several architectural enhancements in the PE to approach lower bound of the CPI. For parallel realization of BLAS and LAPACK, we attach this PE to the Router of REDEFINE. We achieve better area and power performance compared to the yesteryear customized architecture for DLA. Major contributions in architecture in this thesis are as follows: Architecture: We present design of a PE for acceleration of GMM which is a Level-3 BLAS operation We methodically enhance the PE with different features for improvement in the performance of GMM For efficient realization of Linear Algebra Package (LAPACK), we use PE that can efficiently execute GMM and show better performance For further acceleration of LU and QR factorizations in LAPACK, we identify macro operations encountered in LU and QR factorizations, and realize them on a reconfigurable data-path resulting in 25-30% lower run-time