Angelica Lindlöf - Academia.edu (original) (raw)

Papers by Angelica Lindlöf

Planta

MAIN CONCLUSION Enhanced levels of endogenous melatonin in the root of wheat, mainly through the ... more MAIN CONCLUSION Enhanced levels of endogenous melatonin in the root of wheat, mainly through the OMT1 gene, augment the antioxidant system, reestablish redox homeostasis and are associated with combined stress tolerance. A systems biology approach, including a collection of computational analyses and experimental assays, led us to uncover some aspects of a poorly understood phenomenon, namely wheat (Triticum aestivum L.) combined drought and salinity stress tolerance. Accordingly, a cross-study comparison of stress experiments was performed via a meta-analysis of Expressed Sequence Tags (ESTs) data from wheat roots to uncover the overlapping gene network of drought and salinity stresses. Identified differentially expressed genes were functionally annotated by gene ontology enrichment analysis and gene network analysis. Among those genes, O-methyl transferase 1 (OMT1) was highlighted as a more important (hub) gene in the dual-stress response gene network. Afterwards, the potential roles of OMT1 in mediating physiochemical indicators of stress tolerance were investigated in two wheat genotypes differing in abiotic stress tolerance. Regression analysis and correspondence analysis (CA) confirmed that the expression profiles of the OMT1 gene and variations in melatonin content, antioxidant enzyme activities, proline accumulation, H2O2 and malondialdehyde (MDA) contents are significantly associated with combined stress tolerance. These results reveal that the OMT1 gene may contribute to wheat combined drought and salinity stress tolerance through augmenting the antioxidant system and re-establishing redox homeostasis, probably via the regulation of melatonin biosynthesis as a master regulator molecule. Our findings provide new insights into the roles of melatonin in wheat combined drought and salinity stress tolerance and suggest a novel plausible regulatory node through the OMT1 gene to improve multiple-stress tolerant crops.

Supplemental material, sj-xlsx-3-bbi-10.1177_11779322211062722 for The Vulnerability of the Devel... more Supplemental material, sj-xlsx-3-bbi-10.1177_11779322211062722 for The Vulnerability of the Developing Brain: Analysis of Highly Expressed Genes in Infant C57BL/6 Mouse Hippocampus in Relation to Phenotypic Annotation Derived From Mutational Studies by Angelica Lindlöf in Bioinformatics and Biology Insights

Supplemental material, sj-jpg-1-bbi-10.1177_11779322211062722 for The Vulnerability of the Develo... more Supplemental material, sj-jpg-1-bbi-10.1177_11779322211062722 for The Vulnerability of the Developing Brain: Analysis of Highly Expressed Genes in Infant C57BL/6 Mouse Hippocampus in Relation to Phenotypic Annotation Derived From Mutational Studies by Angelica Lindlöf in Bioinformatics and Biology Insights

Supplemental material, sj-xlsx-2-bbi-10.1177_11779322211062722 for The Vulnerability of the Devel... more Supplemental material, sj-xlsx-2-bbi-10.1177_11779322211062722 for The Vulnerability of the Developing Brain: Analysis of Highly Expressed Genes in Infant C57BL/6 Mouse Hippocampus in Relation to Phenotypic Annotation Derived From Mutational Studies by Angelica Lindlöf in Bioinformatics and Biology Insights

Joint International Conference on Information Sciences, 2002

In recent years a number of methods have been proposed for reverse engineering of genetic network... more In recent years a number of methods have been proposed for reverse engineering of genetic networks from gene expression data. These methods work well on small genetic networks with very few connections between genes, but for larger networks and networks with higher connectivity, the computational cost increases dramatically and the performance of these methods is insufficient. In real systems, however, it is known that the networks are large and that genes typically have many interactions. In addition, the methods require abundant expression data for derivation of the networks. A method that can derive networks irrespective of these obstacles and have a low computational cost will be of importance. In this paper, three correlation-based methods are investigated as alternatives. Using correlation-based methods means that the computational cost is reduced, since only N=2 correlations have to be computed for a data set of N expression profiles. The presented methods are not limited by any maximum size of the network, nor by the connectivity of the network, or the amount of expression data.

BMC Genomics, 2007

Background: With the advent of microarray technology, it has become feasible to identify virtuall... more Background: With the advent of microarray technology, it has become feasible to identify virtually all genes in an organism that are induced by developmental or environmental changes. However, relying solely on gene expression data may be of limited value if the aim is to infer the underlying genetic networks. Development of computational methods to combine microarray data with other information sources is therefore necessary. Here we describe one such method. Results: By means of our method, previously published Arabidopsis microarray data from cold acclimated plants at six different time points, promoter motif sequence data extracted from 24,000 Arabidopsis promoters and known transcription factor binding sites were combined to construct a putative genetic regulatory interaction network. The inferred network includes both previously characterised and hitherto un-described regulatory interactions between transcription factor (TF) genes and genes that encode other TFs or other proteins. Part of the obtained transcription factor regulatory network is presented here. More detailed information is available in the additional files. Conclusion: The rule-based method described here can be used to infer genetic networks by combining data from microarrays, promoter sequences and known promoter binding sites. This method should in principle be applicable to any biological system. We tested the method on the cold acclimation process in Arabidopsis and could identify a more complex putative genetic regulatory network than previously described. However, it should be noted that information on specific binding sites for individual TFs were in most cases not available. Thus, gene targets for the entire TF gene families were predicted. In addition, the networks were built solely by a bioinformatics approach and experimental verifications will be necessary for their final validation. On the other hand, since our method highlights putative novel interactions, more directed experiments could now be performed.

Bioinformatics, 2009

Motivation: Cold acclimation involves a number of different cellular processes that together incr... more Motivation: Cold acclimation involves a number of different cellular processes that together increase the freezing tolerance of an organism. The DREB1/CBFs are transcription factors (TFs) that are prominent in the regulation of cold responses in Arabidopsis thaliana, rice and many other crops. We investigated if the expression of DREB1/CBFs and co-expressed genes relies on combinatorial control by several TFs. Our results support this notion and indicate that methods for studying the regulation of complex cellular processes should include identification of combinations of motifs, in addition to searching for individual overrepresented binding sites.

Winter oat, Avena sativa cv. Gerald, was cold acclimated at +4oC for 4, 6, 8 and 32 hours. Total ... more Winter oat, Avena sativa cv. Gerald, was cold acclimated at +4oC for 4, 6, 8 and 32 hours. Total RNA was prepared from these plants, pooled and a cDNA library was constructed. From this library 9792 expressed sequence tags (EST) were sequenced. The average sequence length after vector clipping was 626 bp and the longest sequences were over 900 bp. Clustering and assembly of the these 9792 EST sequences resulted in a set of 4543 sequences. Clustering, assembly and filtering of these sequences resulted in a set of 2866 unique transcripts, denoted the "UniGene" set. Homology searches on publicly available sequence data allowed the assignment of a tentative function to 1622 (57.57%) of these transcripts. Out of the remaining 1246 unclassified sequences, 494 appeared to be oat specific since they lacked any significant sequence similarity (E-values > 1e-10 after BlastX search) to any sequence presently available in the public databases. Genes active in photsynthesis were mos...

Bioinformatics and Biology Insights, 2022

The hippocampus has been shown to have a major role in learning and memory, but also to participa... more The hippocampus has been shown to have a major role in learning and memory, but also to participate in the regulation of emotions. However, its specific role(s) in memory is still unclear. Hippocampal damage or dysfunction mainly results in memory issues, especially in the declarative memory but, in animal studies, has also shown to lead to hyperactivity and difficulty in inhibiting responses previously taught. The brain structure is affected in neuropathological disorders, such as Alzheimer’s, epilepsy, and schizophrenia, and also by depression and stress. The hippocampus structure is far from mature at birth and undergoes substantial development throughout infant and juvenile life. The aim of this study was to survey genes highly expressed throughout the postnatal period in mouse hippocampus and which have also been linked to an abnormal phenotype through mutational studies to achieve a greater understanding about hippocampal functions during postnatal development. Publicly availa...

Motivation: Automated text analysis is an important tool for facilitating the extraction of knowl... more Motivation: Automated text analysis is an important tool for facilitating the extraction of knowledge from biomedical abstracts, thereby enabling researchers to build pathway models that integrate and summarize information from a large number of sources. Advanced methods of in-depth analysis of texts using grammar-based approaches developed within the field of computational linguistics must be adapted to the special requirements and challenges posed by biomedical texts, so that these methods can be made available to the bioinformatics and computational biology communities. Results: Our system for automated text analysis and extraction of pathway information is here applied to a set of PubMed abstracts concerning the CBF signaling pathway, which is a key pathway involved in the cold-adaptation response of plants subjected to cold non-freezing temperatures. The system successfully and accurately rediscovers the main features of this pathway, while also pointing to interesting and plausible new hypotheses. The evaluation also reveals a number of issues which will be important targets in the continued development of the system, e.g. the need for an extended lexicon of taxonomic terms and an improved procedure for recognition of sentence boundaries.

In this work three different approaches for deriving genetic association networks were tested. Th... more In this work three different approaches for deriving genetic association networks were tested. The three approaches were Pearson correlation, an algorithm based on the Boolean network approach and prior knowledge. Pearson correlation and the algorithm based on the Boolean network approach derived associations from gene expression data. In the third approach, prior knowledge from a known genetic network of a related organism was used to derive associations for the target organism, by using homolog matching and mapping the known genetic network to the related organism. The results indicate that the Pearson correlation approach gave the best results, but the prior knowledge approach seems to be the one most worth pursuing

Plant Physiology and Biochemistry

Cell Communication and Signaling

Background Neuroblastoma (NB) is a childhood neural crest tumor. There are two groups of aggressi... more Background Neuroblastoma (NB) is a childhood neural crest tumor. There are two groups of aggressive NBs, one with MYCN amplification, and another with 11q chromosomal deletion; these chromosomal aberrations are generally mutually exclusive. The DLG2 gene resides in the 11q-deleted region, thus makes it an interesting NB candidate tumor suppressor gene. Methods We evaluated the association of DLG2 gene expression in NB with patient outcomes, stage and MYCN status, using online microarray data combining independent NB patient data sets. Functional studies were also conducted using NB cell models and the fruit fly. Results Using the array data we concluded that higher DLG2 expression was positively correlated to patient survival. We could also see that expression of DLG2 was inversely correlated with MYCN status and tumor stage. Cell proliferation was lowered in both 11q-normal and 11q-deleted NB cells after DLG2 over expression, and increased in 11q-normal NB cells after DLG2 silencin...

Physiologia Plantarum

Studying the drought-responsive transcriptome is of high interest as it can serve as a blueprint ... more Studying the drought-responsive transcriptome is of high interest as it can serve as a blueprint for stress adaptation strategies. Despite extensive studies in this area, there are still many details to be uncovered, such as the importance of each gene involved in the stress response as well as the relationship between these genes and the physiochemical processes governing stress tolerance. This study was designed to address such important details and to gain insights into molecular responses of barley (Hordeum vulgare L.) to drought stress. To that, we combined RNA-seq data analysis with field and greenhouse drought experiments in a systems biology approach. RNA-sequence analysis identified a total of 665 differentially expressed genes (DEGs) belonging to diverse functional categories. A gene network was derived from the DEGs, which comprised of a total of 131 nodes and 257 edges. Gene network topology analysis highlighted two programmed cell death (PCD) modulating genes, MC1 (metacaspase 1) and TSN1 (Tudor-SN 1), as important (hub) genes in the predicted network. Based on the field trial, a drought-tolerant and a drought-susceptible barley genotype was identified from eight tested cultivars. Identified genotypes exhibited different physiochemical characteristics, including proline content, chlorophyll concentration, percentage of electrolyte leakage and malondialdehyde content as well as expression profiles of MC1 and TSN1 genes. Machine learning and correspondence analysis revealed a significant relationship between drought tolerance and measured characteristics in the context of PCD. Our study provides new insights which bridge barley drought tolerance to PCD through MC1 and TSN1 pathway.

Molecular Breeding

Understanding how plants respond to salinity stress is essential for developing tolerant genotype... more Understanding how plants respond to salinity stress is essential for developing tolerant genotypes, to keep human food secure since it is threaten by climate changes and increasing population worldwide. Barley (Hordeum Vulgare) is a crop that possesses various salinity tolerance mechanisms that remain to be explored. In this study, data from an RNA-Seq experiment in barley was analyzed to identify changes in genome activities as well as differentially expressed genes (DEGs) in response to salinity stress. A gene network was predicted among identified DEGs and was subjected to network topology analysis, which resulted in the prediction of a hub gene, namely low expression of osmotically responsive gene 2 (LOS2). LOS2 and its two hierarchical downstream genes, salt-tolerant zinc finger (ZAT10) and ascorbate peroxidase1 (APX1), were used in a genome-wide association (GWA) survey to confirm their importance. A field experiment was conducted to recognize susceptible and tolerant genotypes among 10 different barley genotypes based on the principle component analysis (PCA) of stress-related indices. In a separate salinity experiment, two of the genotypes were assessed to assign their physiological and biochemical responses as well as to identify expression profiles of LOS2, ZAT10, and APX1. From the results, the activity of the barley genome was significantly altered toward response to stress. In total, 5692 DEGs were identified and the gene network derived from these genes contained 131 nodes and 257 edges. The identified genotypes clearly showed the difference in water status, osmolyte accumulation, cell membrane damages, and ion homeostasis as well as in expression profiles for studied genes during salinity stress. Our results suggest that LOS2 along with the ZAT10 and APX1 genes may serve as an important part of barley salinity stress tolerance pathways. To our knowledge, this is the first report on the role(s) of LOS2 in barley salinity stress tolerance in a gene network system.

The associative arrays or hashes, as they are also called, are an unordered list of scalar data, ... more The associative arrays or hashes, as they are also called, are an unordered list of scalar data, in opposite to the array that is ordered. Another difference is that the elements are accessed by arbitrary scalars, called keys, and not index numbers. The hash consists of pairs of keys and values, where the key is used to retrieve the associated value from the hash

Bioinformatics and biology insights

The detection of differentially expressed genes from EST data is of importance for the discovery ... more The detection of differentially expressed genes from EST data is of importance for the discovery of potential biological or pharmaceutical targets, especially when studying biological processes in less characterized organisms and where large-scale microarrays are not an option. We present a comparison of five different statistical methods for identifying up-regulated genes through pairwise comparison of EST sets, where one of the sets is generated from a treatment and the other one serves as a control. In addition, we specifically address situations where the sets are relatively small (micro 2,000-10,000 ESTs) and may differ in size. The methods were tested on both simulated and experimentally derived data, and compared to a collection of cold stress induced genes identified by microarrays. We found that combining the method proposed by Audic and Claverie with Fisher's exact test and a method based on calculating the difference in relative frequency was the best combination for ...