Tesis sobre el tema "Transcriptome comparison"

The first chapter of this thesis addresses a common problem in genomics experiments: interpreting a resulting "hit list" of interesting genes. We present work on an approach for summarizing and exploring "hit lists" that makes use of the large amount of gene expression data in public repositories such as the Gene Expression Omnibus. We compare the query list with datasets that we have analyzed for differential expression of genes. Studies that have similarities to the given hit list yield additional insights, help contextualize studies, and serve as a basis for future meta-analysis. A conceptually similar problem that we addressed is the classification or clustering of datasets based on patterns of differential expression. Both problems required a method for determining distances between datasets based on rankings of genes. We tested and benchmarked several methods using manually annotated datasets. The method that performed best according to our evaluation process is based on Kendall's Tau top-k distance. We investigated potential sources of confounds, finding that the largest challenge may be posed by the high prevalence of certain gene expression patterns. These highly prevalent patterns tended to dominate search results. Nonetheless, we demonstrated the effectiveness of this approach in a case study. In the second chapter, we investigated the role of microRNAs in the context of major depression and suicide. We profiled microRNA and messenger RNA levels in post-mortem prefrontal cortex and hippocampus brain tissue of depressed suicides, suicides, and controls. In the prefrontal cortex, we found miR-1202 to be down-regulated in suicides versus controls, and LCT (lactase enzyme) was up-regulated in suicides or depressed suicides compared to controls. The former result was independently confirmed using quantitative PCR. While further study is needed, our results have the potential to provide insight into molecular changes in the brains of depressed and suicidal individuals.

Fusarium Ear Blight is a devastating fungal disease of cereals and due to the contamination of the harvested grain with a range of trichothecene mycotoxins presents a risk to human and animal health. The re-emergence of Fusarium graminearum on wheat and maize, the evolution of more aggressive fungal strains and the lack of an effective control strategy, has increased the need for a greater understanding of the disease aetiology. This project aimed to enhance the understanding of the interaction between F. graminearum and wheat (Triticum aestivum), through the utilisation of microscopy and molecular pathogenomics. A detailed investigation of the infection process revealed a prolonged latent period of intercellular infection that preceded host cell death, intracellular colonisation and the onset of disease symptoms. Phenotypic differences in colonisation and mycotoxin gene expression implied that hyphae within the two phases of infection were transcriptionally distinct, while a bioinformatic analysis described the fungal secretome. The two fungal gene-deficient strains assessed, top1 and tri5, were unable to establish symptomless infection or spread throughout the wheat ear, in the presence or absence of mycotoxin production, suggesting the existence of additional virulence factors. Subsequently, a genome wide transcriptome investigation of the two phases of infection, using both Affymetrix and RNA-sequencing technologies, revealed the unique expression profile, and secretome, of the advancing hyphal front of the symptomless infections. This greater understanding of the biphasic interaction will provide a benchmark for comparison with the single gene deficient strains. Finally, a laser capture microdissection procedure was developed to enable future cell-type specific transcriptome experiments. Collectively, I have discovered and developed a model of how F. graminearum establishes symptomless and symptomatic infection. In doing so, this study has enhanced the understanding of this non-biotrophic pathosystem, providing many new lines of investigation, which could greatly improve crop protection strategies.

Gene expression regulation is dynamic and specific to various factors such as developmental stages, environmental conditions, and stimulation of pathogens. Nowadays, a tremendous amount of transcriptome data sets are available from diverse species. This trend enables us to perform comparative transcriptome analysis that identifies conserved or diverged gene expression responses across species using transcriptome data. The goal of this dissertation is to develop and apply approaches of comparative transcriptomics to transfer knowledge from model species to non-model species with the hope that such an approach can contribute to the improvement of crop yield and human health. First, we presented a comprehensive method to identify cross-species modules between two plant species. We adapted the unsupervised network-based module finding method to identify conserved patterns of co-expression and functional conservation between Arabidopsis, a model species, and soybean, a crop species. Second, we compared drought-responsive genes across Arabidopsis, soybean, rice, corn, and Populus in order to explore the genomic characteristics that are conserved under drought stress across species. We identified hundreds of common gene families and conserved regulatory motifs between monocots and dicots. We also presented a BLS-based clustering method which takes into account evolutionary relationships among species to identify conserved co-expression genes. Last, we analyzed single-cell RNA-seq data from monocytes to attempt to understand regulatory mechanism of innate immune system under low-grade inflammation. We identified novel subpopulations of cells treated with lipopolysaccharide (LPS), that show distinct expression patterns from pro-inflammatory genes. The data revealed that a promising therapeutic reagent, sodium 4-phenylbutyrate, masked the effect of LPS. We inferred the existence of specific cellular transitions under different treatments and prioritized important motifs that modulate the transitions using feature selection by a random forest method. There has been a transition in genomics research from bulk RNA-seq to single-cell RNA-seq, and scRNA-seq has become a widely used approach for transcriptome analysis. With the experience we gained by analyzing scRNA-seq data, we plan to conduct comparative single-cell transcriptome analysis across multiple species.
Doctor of Philosophy
All cells in an organism have the same set of genes, but there are different cell types, tissues, organs with different functions as the organism ages or under different conditions. Gene expression regulation is one mechanism that modulates complex, dynamic, and specific changes in tissues or cell types for any living organisms. Understanding gene regulation is of fundamental importance in biology. With the rapid advancement of sequencing technologies, there is a tremendous amount of gene expression data (transcriptome) from individual species in public repositories. However, major studies have been reported from several model species and research on non-model species have relied on comparison results with a few model species. Comparative transcriptome analysis across species will help us to transform knowledge from model species to non-model species and such knowledge transfer can contribute to the improvement of crop yields and human health. The focus of my dissertation is to develop and apply approaches for comparative transcriptome analysis that can help us better understand what makes each species unique or special, and what kinds of common functions across species have been passed down from ancestors (evolutionarily conserved functions). Three research chapters are presented in this dissertation. First, we developed a method to identify groups of genes that are commonly co-expressed in two species. We chose seed development data from soybean with the hope to contribute to crop improvement. Second, we compared gene expression data across five plant species including soybean, rice, and corn to provide new perspectives about crop plants. We chose drought stress to identify conserved functions and regulatory factors across species since drought stress is one of the major stresses that negatively impact agricultural production. We also proposed a method that groups genes with evolutionary relationships from an unlimited number of species. Third, we analyzed single-cell RNA-seq data from mouse monocytes to understand the regulatory mechanism of the innate immune system under low-grade inflammation. We observed how innate immune cells respond to inflammation that could cause no symptoms but persist for a long period of time. Also, we reported an effect of a promising therapeutic reagent (sodium 4-phenylbutyrate) on chronic inflammatory diseases. The third project will be extended to comparative single-cell transcriptome analysis with multiple species.

The chimpanzee is humankind’s closest living relative and the two species diverged ~6 million years ago. Comparative studies of the human and chimpanzee genomes and transcriptomes are of great interest to understand the molecular mechanisms of speciation and the development of species-specific traits. The aim of this thesis is to characterize differences between the two species with regard to their genome sequences and the resulting transcript profiles. The first two papers focus on indel divergence and in particular, indels causing premature termination codons (PTCs) in 8% of the chimpanzee genes. The density of PTC genes is correlated with both the distance to the telomere and the indel divergence. Many PTC genes have several associated transcripts and since not all are affected by the PTC we propose that PTCs may affect the pattern of expressed isoforms. In the third paper, we investigate the transcriptome divergence in cerebellum, heart and liver, using high-density exon arrays. The results show that gene expression differs more between tissues than between species. Approximately 15% of the genes are differentially expressed between species, and half of the genes show different splicing patterns. We identify 28 cassette exons which are only included in one of the species, often in a tissue-specific manner. In the fourth paper, we use massive parallel sequencing to study the chimpanzee transcriptome in frontal cortex and liver. We estimate gene expression and search for novel transcribed regions (TRs). The majority of TRs are located close to genes and possibly extend the annotations. A subset of TRs are not found in the human genome. The brain transcriptome differs substantially from that of the liver and we identify a subset of genes enriched with TRs in frontal cortex. In conclusion, this thesis provides evidence of extensive genomic and transcriptomic variability between human and chimpanzee. The findings provide a basis for further studies of the underlying differences affecting phenotypic divergence between human and chimpanzee.

The CDC estimated that foodborne infections resulted in approximately 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths per year in the United States (Mead, 1999). There are over 200 known diseases caused by viruses, bacteria, parasites, toxins, metals, or prions that can be transmitted through food. Of these illnesses caused by foodborne disease, the CDC estimates that 38.6 million cases are from identifiable pathogens and 30.9 million of these cases are caused by viruses. Hence, approximately 80% of foodborne illnesses of known etiology result from viral transmission (Mead, 1999). Viral gastrointestinal illness may be caused by virus families such as: enterovirus, rotavirus, calicivirus, astrovirus, or norovirus. These viruses are highly contagious and are spread through the fecal-oral route; transmission vehicles include contaminated food or beverages, infected food handlers, fomites or close contact with an infected individual (FDA Bad Bug Book, 2003). Until recently, there have been few studies concentrating on viruses found in or on foods. There are several technical difficulties that hinder progress in detecting viral agents from foods. One of these problems is the presence of matrix inhibitors. Substances responsible for matrix inhibition include humic acid, polysaccharides, myoglobins, metal ions, glycogen, and lipids (Monpoeho, 2001). These substances in foods produce smearing of the RT-PCR amplicon bands on agarose gels. Several methods to reduce inhibitory compounds utilize multiple toxic reagents in the procedure. In this study, varying centrifugal forces were tested at different steps of the virus extraction/concentration procedure to reduce matrix inhibitory effects for molecular detection of norovirus and poliovirus seeded onto food surfaces. This method incorporates the rapid detection capabilities of RT-PCR with the ability to reduce or eliminate matrix inhibitors present in food, by altering the centrifugal force. Results for both viruses showed that band intensity decreased as the viral concentration decreased and no one method was superior for all food matrices. This investigation showed that matrix specific modifications to the basic protocol are required to efficiently extract viruses from the surface of foods. Each food should be assessed to determine modifications to the standard method that would be optimal for viral concentration and extraction.

Lo sviluppo della bacca di vite può essere descritto come una successione di cambiamenti fisiologici e biochimici che riflettono la modulazione trascrizionale di molti geni. Nello scorso decennio molti studi trascrittomici sono stati eseguiti per descrivere in modo più approfondito questo processo di sviluppo dinamico e complesso. Tuttavia, la maggior parte di questi studi trascrittomici si sono focalizzati solo su un’unica varietà per volta e quindi vi è ancora una mancanza di risorse per poter effettuare comparazioni sullo sviluppo della bacca in differenti varietà di vite. Questa tesi riguarda la prima comparazione del trascrittoma della bacca di vite effettuato attraverso RNA sequencing di 120 campioni di RNA, corrispondenti alle bacche di dieci varietà raccolte a quattro stadi fenologici, due precedenti e due successivi all’invaiatura, in triplicato biologico. Quest’analisi RNA-seq ha mostrato un’evidente e profonda transizione del trascrittoma dalla fase verde alla maturazione che avviene all’invaiatura indipendentemente da colore della buccia e varietà, che coinvolge la soppressione di diversi processi metabolici relativi alla crescita vegetativa, e l’induzione di solo poche vie, come processi di metabolismo secondario e di risposta a stimoli biotici. Questo importante riprogramma del trascrittoma durante la maturazione è stato evidenziato da diversi approcci: correlazione con distanza di Pearson, analisi a componenti principali (PCA), O2PLS-DA, ricerca di biomarcatori, analisi clustering e network di correlazione. La creazione della prima via trascrittomica di sviluppo della bacca di vite, corrispondente a geni aventi un profilo di espressione simile durante tutto lo sviluppo indipendentemente dalla varietà, ha permesso di identificare geni coinvolti nei maggiori processi biologici che avvengono durante la maturazione del frutto. Infine, l’espressione dei geni appartenenti alla via biosintetica dei fenilpropanoidi/flavonoidi si sono mostrati insufficienti da soli nello spiegare le differenze trascrittomiche tra varietà rosse e bianche; tuttavia si presuppone che questi – probabilmente per effetto dell’accumulo di antociani nella buccia della bacca dall’inizio della maturazione – influenzino comunque il programma della fase di maturazione, determinando il coinvolgimento e reclutamento di geni appartenenti ad altri processi biologici.
Grape berry development can be described as a succession of physiological and biochemical changes reflecting the transcriptional modulation of many genes. In the last decade, many transcriptomic studies have been carried out to deeper describe this dynamic and complex development. Nonetheless, most of those transcriptomic studies focused on one single variety at a time and then there is still a lack of resources for comparing berry development in different grape varieties. This thesis describes the first berry transcriptome comparison carried out by RNA sequencing of 120 RNA samples, corresponding to 10-variety berries collected at four phenological growth stages, two pre- and two post-véraison, in biological triplication. This RNA-Seq analysis showed an evident deep green-to-maturation transcriptome shift occurring at véraison independently on skin colour and variety, which involves the suppression of diverse metabolic processes related to vegetative growth, and the induction of only a few pathways, such as secondary metabolic processes and responses to biotic stimuli. This fundamental transcriptome reprogramming during ripening was highlighted by distinct approaches: Pearson’s correlation distance, PCA, O2PLS-DA, biomarker discovery, clustering analysis and correlation network method. The establishment of the first grape berry development transcriptomic route, corresponding to the genes having similar patterns of expression during whole development independently on the variety, allowed identifying genes involved in the main biological processes occurring during berry development. Finally, the expression of phenylpropanoid/flavonoid biosynthetic pathway-related genes was found to be insufficient by itself to explain the differences between red- and white-grape transcriptomes, however it was supposed to influence – supposedly by the effect of anthocyanins accumulation in berry skin since the onset of ripening – maturation-phase transcriptional program, determining the recruitment of genes belonging to other biological processes.

Title page, abstract and table of contents only. The complete thesis in print form is available from the University of Adelaide Library.
Studying the interaction between grapevines and the environment may provide insights of how terroir drives unique characters in wine. Analysing changes in gene expression between different environmental conditions provides a first step in understanding genes that may play a role in grapevine adaption. We, therefore, carried out RNA-seq analysis on Shiraz grapevine leaf tissue harvested from two sub-regions of the Barossa Valley to investigate whether gene expression changes occurred in response to two important environmental factors for plant growth, temperature and elevation. Young leaves from three vineyards in the Barossa central ground and three in the Eden Valley were sampled at budburst. The transcriptome profiling of all samples was clustered by vineyard and separated by region. In total, 429 genes showed significant changes in gene expression between two regions (FDR < 0.001). Among the differentially expressed genes, we found a subset of genes enriched in Gene Ontology (GO) terms that are related to environmental response, including abiotic stress and external biotic stress (Q-value < 0.05). Our study provides preliminary analysis of transcriptome changes in different sub-regions of Barossa Valley and identified potential candidate genes involved in adaptive responses under different environmental condition.
Thesis (M.Bio.(PB)) -- University of Adelaide, Masters of Biotechnology (Plant Biotechnology), School of Agriculture, Food and Wine, 2016

碩士
輔仁大學
生命科學系碩士班
106
Pseudoregma bambucicola Takahashi is a social aphid characterized with host alternation and gall formation. It reproduces pathenogenetically in most of the generations within a life cycle. It also performs very complex polyphenism. During the process of host alternation, P. bambucicola utilizes Styrax suberifolius as its primary host plant and forms the gall to live and feed inside. Bamboos are used as its secondary host plant and P. bambucicola prefers to feed on the surface of the bamboo stem. On both the primary and the secondary host plants, P. bambucicola produces wingless females, winged females and soldiers. Among all these three types of aphids, soldiers are the most specialized morphs because it is sterile and with specialized defensive morphology and behavior. To uncover the molecular level characteristics of soldiers and non-soldiers, we compared the Next Generation Sequencing based transcriptome data between soldiers and wingless adults from both kinds of host plants. Weighted deviation was used to filter those differentially expressed genes. GO (Gene Ontology) enrichment was used to analyze the significantly expressed GO annotation. Finally, WEGO (Web Gene Ontology Annotation Plot) was used to compare and plot GO annotation results. We found 300~800 differentially expressed genes from different combinations of comparisons. After deleting genes without GO annotations, there were 100~300 differentially expressed genes left. After GO significance analysis and classification, we found that some genes classified within the category of Structural Molecular Activity are related to cuticle composition. We found that soldiers and wingless adults of P. bambucicola both have specific differentially expressed genes within the category of structural constituent of cuticle. Aphids from different host plants also reveal specific differentially expressed genes within the category of structural constituent of cuticle. In conclusion, we found that soldiers, regardless of host plants, of P. bambucicola have a specific differentially expressed gene which is related to cuticle constitution, and soldiers on bamboos have a specific differentially expressed gene which is related to muscle constitution.

碩士
國立臺灣大學
生物產業機電工程學研究所
103
The revolutionary advances of next-generation sequencing technology not only provide high-throughput sequencing data, but also considerably facilitate studies with regard to transcriptome without a reference genome. By means of de novo assembly, assembled transcripts can be retrieved from the sequencing reads. In order to infer the protein function of the assembled sequences, one conventional approach is to utilize the sequence similarity against the protein database by BLASTx. In this study, only 49% (approximately 24,800 sequences) of the assembled Bactrocera dorsalis (B. dorsalis) sequences can be annotated with Drosophila melanogaster (D. melanogaster) genes by BLASTx. For Bactrocera cucurbitae (B. cucurbitae), it is only 46% (approximately 25,400 sequences) of the assembled transcripts which can be annotated with D. melanogaster genes. It reveals an inevitable limitation when the target organism is evolutionarily distant from the model organism. Compared to the traditional approach, if the process of similarity comparison is not only against the most relative model organism, but also utilizes the assistance of much more closely-relative organism, it can further enhance the completeness of the annotation list. B. cucurbitae and B. dorsalis belong to the same genus, and share a high level of homology to each other. With the procedure of finding connected components (CCs), we can utilize the linkage of the similarity information from these two species for further improvement of annotation. On the other hand, the statistics of the assembly result has shown that the average length of B. cucurbitae assembled sequences is twice longer than that of B. dorsalis, suggesting that the assembly of B. dorsalis may contain much more incompletely assembled transcripts than the assembly of B. cucurbitae. Under the procedure of CCs analysis, we can leverage the CCs to improve the de novo assembly result, by providing a list of transcripts that could have been intrinsically joined together. A total of 7,086 CCs was obtained by using a strict criteria of the similarity parameters (identity higher than 80%, E-value smaller than 10-20 and alignment length longer than 70 amino acids). With the assistance of the mutually comparison among the sequences with the same Bactrocera genus, it suggested the potential annotation of the transcripts that cannot be provided when the transcripts are only compared with D. melanogaster sequences. For increasing the completeness of the annotation list, there are 925 B. dorsalis sequences and 272 B. cucurbitae sequences that can be additionally annotated with D. melanogaster genes. As well, for further improvement toward de novo assembly, a total of 1,919 B. dorsalis sequences are recommended to be concatenated into 680 longer transcripts. Similarly, a total of 71 B. cucurbitae sequences are suggested to be joined into 52 longer transcripts. Finally, a database was constructed to provide a user-friendly platform for the CC analysis and to assist the biologists retrieving the illustration of the relationship of sequence alignment within CCs.

碩士
國立臺灣海洋大學
資訊工程學系
100
The technologies of high-throughput sequencing exploited dynamic complementary DNA sequencing in an approach termed RNA-seq. The RNA-seq data was used not only to analyze the unknown genes or functions from incomplete sequencing genome but also to observe the mutation of gene differential expression from multiple transcriptomes sequenced at different time points or among different strains. However, most RNA-seq analyses focused on evaluating the amount of recognized genes or embracing a small set of genes related to a selected function at a time. Therefore, some important associated information might be ignored due to limited analytical scale of gene analysis. Hence, we developed an integrated system to analyze transcriptomic data by featuring some functional classification methods including gene ontology (GO), biological pathway and protein domain/family. The developed system could annotate and cluster the assembled contigs from various species and visualize the functional relationship through systems biology representation for cross-species comparison. In addition, analysis of differential gene expression among various RNA-seq experiments based on read coverage account is also proposed in this system. First, to avoid the bias from gene expression level among various experiments, the conserved homologous housekeeping genes and their corresponding coverage counts were selected as standards for performing normalization procedures. Then, the variations of gene expression were annotated, compared, and visualized by several statistical graphs in terms of systems biology representation. Finally, the assembled contigs could be analyzed in details by using an integrated and comprehensive bioinformatics system (BiMFG), which system includes information retrieval function for comparing with marine and freshwater related model species and it also provides analytical tools at different levels of biological sequence including: primary sequences, secondary structures and tertiary structures.

Two immunologically distinct strains of poultry coccidium Eimeria maxima, Guelph (GS) and M6 strains, were investigated. Paired in vivo experiments demonstrated that GS and M6 have prepatent periods of approximately 120 h followed by peak oocyst shedding at 144 150 h post inoculation. Fecundity of E. maxima M6 (12.8×103±1.95 oocysts shed/oocyst inoculated) was approximately twice that of GS (6.9×103±3.33) when inoculated with 1×103 infective oocysts per bird. Numerous sequential observations of synchronized populations of oocysts sporulating at 26°C showed no difference in the sporulation kinetics of the two strains; in both strains, sporogony was divided into five morphologically distinguishable stages whose abundance peaked at the following times during sporulation: unsporulated oocysts at 0 h; sporoblast anlagen at 18 h; sporoblasts without sporocyst walls at 22 h; and sporocysts without mature sporozoites at 38 h. Total RNA was isolated from four stages of sporogonic development (18 h, 22 h and 38 h of sporulation, and excysting sporozoites). These RNA samples were quantitatively pooled from each strain separately prior to selection of poly A mRNA that was then fragmented, end-labeled and pyrosequenced using an Illumina HiSeq 2000 sequencer. The resulting transcriptome sequences (~48.8×109bp total reads) were paired and de novo assembled. Ten thousands transcripts (5,000 from each strain) were searched against GenBank using blastx. A total of 2,067 transcripts of GS and 1,610 transcripts of M6 were assigned to putative biological function; ~60% of functionally annotated transcripts mapped to metabolic or cellular processes. GPI anchored surface antigens (SAgs) identified in GS (18 SAgs) and M6 (18 SAgs) belonged to four major multi copy gene families and 2 single copy loci. Relative expression of SAgs expressed by both strains was generally similar; however, 3 GPI-anchored SAgs were uniquely expressed by each of GS and M6. One multigene locus demonstrated strain-specific SAg expression that may explain the lack of cross immunity between these strains. This represents the first transcriptome data of sporulation of E. maxima and first comparison of immunologically distinct strains of any Eimeria sp. These data should aid in the search for antigenic targets that could be included in future subunit vaccines against these important agricultural parasites.
Research Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Ministry of Agriculture and Food (OMAF); Funding of Studies: Iraqi Ministry of Higher Education and Scientific Research (MOHESR) for PhD scholarship support; American Society of Parasitologists for a Marc Dresden Travel Award to attend the 2012 ASP Annual Meeting.

abstract: Induced pluripotent stem cells (iPSCs) are an intriguing approach for neurological disease modeling, because neural lineage-specific cell types that retain the donors' complex genetics can be established in vitro. The statistical power of these iPSC-based models, however, is dependent on accurate diagnoses of the somatic cell donors; unfortunately, many neurodegenerative diseases are commonly misdiagnosed in live human subjects. Postmortem histopathological examination of a donor's brain, combined with premortem clinical criteria, is often the most robust approach to correctly classify an individual as a disease-specific case or unaffected control. We describe the establishment of primary dermal fibroblasts cells lines from 28 autopsy donors. These fibroblasts were used to examine the proliferative effects of establishment protocol, tissue amount, biopsy site, and donor age. As proof-of-principle, iPSCs were generated from fibroblasts from a 75-year-old male, whole body donor, defined as an unaffected neurological control by both clinical and histopathological criteria. To our knowledge, this is the first study describing autopsy donor-derived somatic cells being used for iPSC generation and subsequent neural differentiation. This unique approach also enables us to compare iPSC-derived cell cultures to endogenous tissues from the same donor. We utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, supported by (i) a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P < 0.05), consistent with the transcriptional complexity of the brain, (ii) an increase in CpG methylation after neural differentiation that resembled the epigenomic signature of the endogenous tissue, and (iii) a significant decreasing monotonic correlation between the days of our timecourse and the percent of in vitro to brain-tissue differences (P < 0.05) for tissue-specific protein-coding genes and all putative lincRNAs. These studies support the utility of autopsy donors' somatic cells for iPSC-based neurological disease models, and provide evidence that in vitro neural differentiation can result in physiologically progression.
Dissertation/Thesis
Ph.D. Molecular and Cellular Biology 2013