Papers by Christian Iseli

PLOS ONE
All life forms on earth ultimately descended from a primordial population dubbed the last univers... more All life forms on earth ultimately descended from a primordial population dubbed the last universal common ancestor or LUCA via Darwinian evolution. Extant living systems share two salient functional features, a metabolism extracting and transforming energy required for survival, and an evolvable, informational polymer–the genome–conferring heredity. Genome replication invariably generates essential and ubiquitous genetic parasites. Here we model the energetic, replicative conditions of LUCA-like organisms and their parasites, as well as adaptive problem solving of host-parasite pairs. We show using an adapted Lotka-Volterra frame-work that three host-parasite pairs–individually a unit of a host and a parasite that is itself parasitized, therefore a nested parasite pair–are sufficient for robust and stable homeostasis, forming a life cycle. This nested parasitism model includes competition and habitat restriction. Its catalytic life cycle efficiently captures, channels and transform...
Heatmap of the top 50 genes from the luminal-specific and myoepithelial-specific transcriptomes
<b>Copyright information:</b>Taken from "Establishment of the epithelial-specifi... more <b>Copyright information:</b>Taken from "Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data"Breast Cancer Research 2006;8(5):R56-R56.Published online 2 Oct 2006PMCID:PMC1779497. Genes were ranked in order of fold change (myoepithelial over luminal) for each platform separately after which a median rank over all four platforms was determined. Genes are listed with their human transcriptome database (HTR) cluster, HUGO Name, description and UniGene and RefSeq identifiers. Green corresponds to luminal-type; red to myoepithelial-type; black indicates no corresponding microarray feature. Expression measurements obtained by: 1, Agilent; 2, 20 k brk; 3, CodeLink; 4, Affymetrix platform.
Distribution of 3' EST tags in human and genomes
<b>Copyright information:</b>Taken from "Similarities and differences of polyade... more <b>Copyright information:</b>Taken from "Similarities and differences of polyadenylation signals in human and fly"BMC Genomics 2006;7():176-176.Published online 12 Jul 2006PMCID:PMC1574307. A: Distribution of trusted tags per gene. In both species, the distribution of tags per gene follows a power law, with similar exponents (-2.29 for human tags and -2.05 for tags). B: 3'UTR length distributions, in human and Drosophila genes, the average length for humans is 995 bp, for it is 200 bp. Each point is the number of 3'UTRs of given length. C: Number of polyadenylation clusters in genes having more than 1 cluster, human genes have up to 25 separate 3P clusters (mean number of clusters per human gene is 2, 3, for drosophila genes 1.11).
Functional classification of the differentially expressed epithelial tumour transcriptome
<b>Copyright information:</b>Taken from "Establishment of the epithelial-specifi... more <b>Copyright information:</b>Taken from "Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data"Breast Cancer Research 2006;8(5):R56-R56.Published online 2 Oct 2006PMCID:PMC1779497. The top 15 biological processes showing overall up-regulation and down-regulation are shown. The biological processes are ranked from top to bottom according to their ascending value as described in the Materials and methods. The numbers of genes within each process that are up-regulated or down-regulated for each category are also shown as black and grey bars, respectively.
Nuclease Target Sites
ZFN-Site searches genomes for zinc finger nuclease target sites and off-target sites Cradick et a... more ZFN-Site searches genomes for zinc finger nuclease target sites and off-target sites Cradick et al. Cradick et al. BMC Bioinformatics 2011, 12:152

Comparison of massively parallel signature sequencing (MPSS) data with microarray analysis
<b>Copyright information:</b>Taken from "Establishment of the epithelial-specifi... more <b>Copyright information:</b>Taken from "Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data"Breast Cancer Research 2006;8(5):R56-R56.Published online 2 Oct 2006PMCID:PMC1779497. Differentially expressed gene profiles from MPSS (100%) were overlaid with each microarray platform individually. Percentage of coverage (light grey) and concordance in differential expression between MPSS and individual arrays (dark grey) are shown together with the combined coverage and confirmation by at least one array (1 platform). Enumeration of the differentially expressed transcripts detected by "MPSS-only", by "MPSS and array", and those transcripts reported as differential by at least two arrays, but not by MPSS ("Array only"). The results obtained by RT-PCR for these subgroups are shown below (see Additional file 6).

Plant Physiology, 2019
Cis-Natural Antisense Transcripts (cis-NATs), which overlap protein coding genes and are transcri... more Cis-Natural Antisense Transcripts (cis-NATs), which overlap protein coding genes and are transcribed from the opposite DNA strand, constitute an important group of noncoding RNAs. Whereas several examples of cis-NATs regulating the expression of their cognate sense gene are known, most cis-NATs function by altering the steady-state level or structure of mRNA via changes in transcription, mRNA stability, or splicing, and very few cases involve the regulation of sense mRNA translation. This study was designed to systematically search for cis-NATs influencing cognate sense mRNA translation in Arabidopsis (Arabidopsis thaliana). Establishment of a pipeline relying on sequencing of total polyA + and polysomal RNA from Arabidopsis grown under various conditions (i.e. nutrient deprivation and phytohormone treatments) allowed the identification of 14 cis-NATs whose expression correlated either positively or negatively with cognate sense mRNA translation. With use of a combination of cis-NAT stable over-expression in transgenic plants and transient expression in protoplasts, the impact of cis-NAT expression on mRNA translation was confirmed for 4 out of 5 tested cis-NAT:sense mRNA pairs. These results expand the number of cis-NATs known to regulate cognate sense mRNA translation and provide a foundation for future studies of their mode of action. Moreover, this study highlights the role of this class of noncoding RNAs in translation regulation.
Immunohistochemical analysis of periostin (POSTN), IL8 and cartilage oligomeric matrix protein (COMP)
<b>Copyright information:</b>Taken from "Establishment of the epithelial-specifi... more <b>Copyright information:</b>Taken from "Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data"Breast Cancer Research 2006;8(5):R56-R56.Published online 2 Oct 2006PMCID:PMC1779497. POSTN-positive invasive ductal carcinoma (IDC; ×400), in which both epithelial and stromal cells show cytoplasmic expression. POSTN-negative IDC in which only the spindle shaped stromal cells are stained (×400). IL8 (×100), showing positive staining only in the malignant breast epithelial cells. COMP expression in the epithelial and stromal cells of an IDC, showing strong expression in both stromal and epithelial cells (×100).
Cumulative Kaplan-Meier curves for epithelial expression of periostin (POSTN)
<b>Copyright information:</b>Taken from "Establishment of the epithelial-specifi... more <b>Copyright information:</b>Taken from "Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data"Breast Cancer Research 2006;8(5):R56-R56.Published online 2 Oct 2006PMCID:PMC1779497. A cohort of poor-prognosis estrogen receptor (ER)-positive tumours was analysed showing: a significantly shorter overall survival (= 0.0083); a shorter disease free survival (= 0.0136).
Position and consensus sequence for PAS and DSE identified in Human and cleavage site sequence tags (A)
<b>Copyright information:</b>Taken from "Similarities and differences of polyade... more <b>Copyright information:</b>Taken from "Similarities and differences of polyadenylation signals in human and fly"BMC Genomics 2006;7():176-176.Published online 12 Jul 2006PMCID:PMC1574307. Dotted lines: Windows defining the subset of motifs used for the final weight matrix determination, pos 24–38 for PAS and 51–75 for DSE (CS is at position 50). B-E: sequence logos for the inferred weight matrices. B: Human PAS. C: Human DSE. D: polyadenylation signal. E: DSE.
Details
Performs multi-threaded base calling on a collection of intensity files generated by the Solexa i... more Performs multi-threaded base calling on a collection of intensity files generated by the Solexa image analysis software
License GPL-2
1 # # S4 method for signature ’RolexaRun’
Research article Similarities and differences of polyadenylation signals in human and fly
Cell Reports, 2021
Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immun... more Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING Graphical abstract Highlights d STING and type I IFN pathway activation leads to T cell infiltration in BRCA1 mut OC d STING drives VEGF-A upregulation in BRCA1 mut tumor cells d STING loss reduces angiogenesis, boosts CD8 T cells, and reverts dual ICB resistance d Anti-VEGF-A, PARPis, and dual ICB combination control Brca1 À/À tumor growth in vivo

Nature communications, Mar 15, 2018
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mut... more Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8 T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition is discordant between circulating T cells and TILs, and is more likely to be found among TILs, which display higher functional avidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8 T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based ...
Clinical Genetics, 2013
targeted high-throughput sequencing for Mendelian cardiac disorders.
Cell, 2020
Highlights d Diverse neoantigen predictions on shared genomic data from a global consortium d 37 ... more Highlights d Diverse neoantigen predictions on shared genomic data from a global consortium d 37 out of 608 tested peptide-MHCs are bound by patientmatched T cells d Epitope presentation and recognition characteristics predict immunogenicity d Model-based interventions improve neoantigen prediction
BICC-UNIL-EPFL/randomizer: v1.0
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Rapid evolution of cancer/testis genes on the X chromosome-0
<b>Copyright information:</b>Taken from "Rapid evolution of cancer/testis genes ... more <b>Copyright information:</b>Taken from "Rapid evolution of cancer/testis genes on the X chromosome"http://www.biomedcentral.com/1471-2164/8/129BMC Genomics 2007;8():129-129.Published online 23 May 2007PMCID:PMC1890293.ervals A-I is shown. The categories are: CT-X, CT genes on chromosome X (N = 33); CT-nonX, CT genes not on chromosome X (N = 49); Control-X, control genes on chromosome X (N = 64); Control-nonX, control genes not on chromosome X (N = 71). The intervals are: 0 ≤ A ≤ 0.25; 0.25 &lt; B ≤ 0.5; 0.5 &lt; C ≤ 0.75; 0.75 &lt; D ≤ 1.0; 1.0 &lt; E ≤ 1.25; 1.25 &lt; F ≤ 1.5; 1.5 &lt; G ≤ 1.75; 1.75 &lt; H ≤ 2; 2 &lt; I ≤ 4. Genes which had no synonymous changes (dN/dS denoted '∞' in Table 2) were omitted from the analysis.

Background: Viral infections are the leading cause of childhood acute febrile illnesses motivatin... more Background: Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Untargeted metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Results: Here, we describe the blood virome of 816 febrile children (<5 years) presenting at outpatient departments in Dar es Salaam over one-year. We show that half the population (394/816) had at least one detected virus recognized as causes of human infection/disease (13.8% enteroviruses (enterovirus A, B, C, and rhinovirus A and C), 12% ro...
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Papers by Christian Iseli