Feilman Fellow; Program Head, Precision Health and Team Lead, Computational Biology
BSc (Hons) MSc PhD
Timo Lassmann, B.Sc. Biotechnology (1999), MSc Bioinformatics (2001), PhD functional genomics (2006), Karolinska Institute Sweden, has a major interest in computational biology and genomics.
During his PhD he published a series of innovative algorithms to analyze biological sequences still heavily used to this day (6 first author papers; cited 1000+ times; median 135 times). In parallel, he led the data analysis in several collaborative studies involving laboratory groups. Finally he contributed to the PFAM consortium, a self-updating database of protein domain families.
In 2006 he moved to RIKEN, Japan, where he transitioned into leadership roles in the international Functional ANnotation of The Mammalian Genome - FANTOM4 (3x Nature Genetics, 2009) and FANTOM5 project (3x Nature, 2014 - 2017, Science 2015). He managed a team of 4-8 staff to perform all primary data analysis tasks on these large projects involving 250 collaborators and thousands of datasets. Between 2009 - 2012 he was a lead analyst in the ENCyclopedia Of DNA Elements (ENCODE) project (2x Nature, 2012). At RIKEN he also led a small but productive algorithm development team and an industrial collaboration unit. He is still actively involved in the next iteration of the FANTOM project focussed on deciphering the role of non-coding elements in the human genome.
In 2014, Timo Lassmann was appointed as the head of computational biology at the Telethon Kids Institute, Australia. The focus of his research lab is to re-purpose big “omics” data in translational projects to improve the well-being of children suffering from cancers and rare diseases. In 2017 he was appointed the leader of the Genetics and Rare Disease program, initiated a precision medicine project and was awarded the Feilman Fellowship in genomics.
He is now the Program Head of the Precision Health team.
In total Timo published 90+ publications in peer reviewed journals, which are cited 25963 times with a h-index of 39 (as reported by google scholar).
Find Timo on Google Scholar
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Projects
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Publications
January 2024
CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction
An estimated 3.5%-5.9% of the global population live with rare diseases, and approximately 80% of these diseases have a genetic cause. Rare genetic diseases are difficult to diagnose, with some affected individuals experiencing diagnostic delays of 5-30 years. Next-generation sequencing has improved clinical diagnostic rates to 33%-48%. In a majority of cases, novel variants potentially causing the disease are discovered.
Autism Spectrum Published research Computational Biology Translational Genetics Child disability Rare diseases GeneticsDecember 2023Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease
Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays.
Published research Early Childhood Development Computational Biology Child Physical Activity, Health and Development Mitochondrial Research Translational Genetics Genomics Child and adolescent health GeneticsJanuary 2023SAMStat 2: quality control for next generation sequencing data
SAMStat is an efficient program to extract quality control metrics from fastq and SAM/BAM files. A distinguishing feature is that it displays sequence composition, base quality composition and mapping error profiles split by mapping quality. This allows users to rapidly identify reasons for poor mapping including the presence of untrimmed adapters or poor sequencing quality at individual read positions.
Published research Computational BiologyDecember 2022CD4+ T cells drive an inflammatory, TNF-α/IFN-rich tumor microenvironment responsive to chemotherapy
While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize the chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, and compare the gene expression profiles of responders with progressors.
Children's Cancers Published research Computational Biology Sarcoma Translational Research Translational GeneticsSeptember 2021Temporally restricted activation of IFNβ signaling determines response to immune checkpoint therapy
The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients.
Children's Cancers Published research Computational Biology Sarcoma Translational Research Translational GeneticsFebruary 2022An expanded phenotype centric benchmark of variant prioritisation tools
Identifying the causal variant for diagnosis of genetic diseases is challenging when using next-generation sequencing approaches and variant prioritization tools can assist in this task. These tools provide in silico predictions of variant pathogenicity, however they are agnostic to the disease under study. We previously performed a disease-specific benchmark of 24 such tools to assess how they perform in different disease contexts.
Published research Computational BiologyNovember 2021Common and Rare Genetic Variants That Could Contribute to Severe Otitis Media in an Australian Aboriginal Population
Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians.
Published research Ear Infections Aboriginal Health Computational Biology Genetics and HealthFebruary 2022Functional validation of variants of unknown significance using CRISPR gene editing and transcriptomics: A Kleefstra syndrome case study
There are an estimated > 400 million people living with a rare disease globally, with genetic variants the cause of approximately 80% of cases. Next Generation Sequencing (NGS) rapidly identifies genetic variants however they are often of unknown significance.
Published research Computational Biology Translational GeneticsNovember 2021The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution
The bone marrow microenvironment plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.
Children's Cancers Published research Academic Biostatistics Leukaemia Translational Research Systems VaccinologyFebruary 2022CRISPR single base editing, neuronal disease modelling and functional genomics for genetic variant analysis: pipeline validation using Kleefstra syndrome EHMT1 haploinsufficiency
Over 400 million people worldwide are living with a rare disease. Next Generation Sequencing identifies potential disease causative genetic variants. However, many are identified as variants of uncertain significance and require functional laboratory validation to determine pathogenicity, and this creates major diagnostic delays.
Published research Computational Biology Translational GeneticsSeptember 2021Searching for a technology-driven acute rheumatic fever test: the START study protocol
The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus.
Published research Rheumatic Heart Disease Systems Immunology Group A Streptococcal & Rheumatic Heart Disease Computational Biology Systems VaccinologyFebruary 2021Zika Virus Changes Methylation of Genes Involved in Immune Response and Neural Development in Brazilian Babies Born With Congenital Microcephaly
The recent increase in babies born with brain and eye malformations in Brazil is associated with Zika virus (ZIKV) infection in utero. ZIKV alters host DNA methylation in vitro. Using genome-wide DNA methylation profiling we compared 18 babies born with congenital ZIKV microcephaly with 20 controls. We found ZIKV-associated alteration of host methylation patterns, notably at RABGAP1L which is important in brain development, at viral host immunity genes MX1 and ISG15, and in an epigenetic module containing the causal microcephaly gene MCPH1. Our data support the hypothesis that clinical signs of congenital ZIKV are associated with changes in DNA methylation.
Published research Academic Biostatistics Infectious Diseases Genetics and HealthDecember 2020A flexible computational pipeline for research analyses of unsolved clinical exome cases
Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar.
Published research Computational Biology Genetics and HealthNovember 2020The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution
The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.
Children's Cancers Published research Leukaemia Translational Research Subsite: Cancer Translational Genomics in LeukaemiaOctober 2020Characteristics of TCR Repertoire Associated With Successful Immune Checkpoint Therapy Responses
Immunotherapies have revolutionized cancer treatment. In particular, immune checkpoint therapy (ICT) leads to durable responses in some patients with some cancers. However, the majority of treated patients do not respond. Understanding immune mechanisms that underlie responsiveness to ICT will help identify predictive biomarkers of response and develop treatments to convert non-responding patients to responding ones. ICT primarily acts at the level of adaptive immunity. The specificity of adaptive immune cells, such as T and B cells, is determined by antigen-specific receptors.
Children's Cancers Published research Sarcoma Translational ResearchOctober 2020Reference exome data for a Northern Brazilian population
Exome sequencing is widely used in the diagnosis of rare genetic diseases and provides useful variant data for analysis of complex diseases. There is not always adequate population-specific reference data to assist in assigning a diagnostic variant to a specific clinical condition.
Published research Early Childhood Development Genetics and HealthJune 2020Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows
Systematic comparison of recovered cell types and their transcriptional profiles across the workflows has highlighted protocol-specific biase
Published research Computational BiologyMay 2020Bilateral murine tumor models for characterizing the response to immune checkpoint blockade
This protocol describes bilateral murine tumor models that display a symmetrical yet dichotomous response to immune checkpoint blockade
Children's Cancers Published research Systems Immunology Computational Biology Sarcoma Translational ResearchApril 2020Reference exome data for Australian Aboriginal populations to support health-based research
Our data set provides a useful reference point for genomic studies on Aboriginal Australians
Published research Aboriginal Health Group A Streptococcal & Rheumatic Heart Disease Computational Biology Genetics and HealthDecember 2019Expression Levels of Therapeutic Targets as Indicators of Sensitivity to Targeted Therapeutics
We investigated the relationship between the sensitivity of hundreds of cell lines to hundreds of drugs, and the relative expression levels of the targets
Published research Computational BiologyNovember 2019Personalised analytics for rare disease diagnostics
Here we focus on the problem of prioritising variants with respect to the observed disease phenotype
Published research Computational Biology Genetics and HealthSeptember 2019Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis
The FANTOM5 cerebellum time series is a high-quality transcriptome database for functional investigation of gene regulatory networks in cerebellar development
Published research Computational BiologyAugust 2019Antisense Transcription in Loci Associated to Hereditary Neurodegenerative Diseases
Evidence for the existence of additional regulatory mechanisms of the expression of neurodegenerative disease-causing genes by antisense long noncoding RNAs
Published research Computational BiologyJuly 2019Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment
Our results identify a pretreatment tumor microenvironment that predicts response to immune checkpoint blockade, which can be therapeutically attained
Children's Cancers Published research Systems Immunology Computational Biology Sarcoma Translational ResearchJune 2019Functional genomics in cancer immunotherapy: Computational approaches for biomarker and drug discovery
This review explores computational strategies to yield biological insight into the processes involved in the immunotherapeutic response
Children's Cancers Published research Computational Biology Sarcoma Translational ResearchMay 2019Tricho-hepatic-enteric syndrome (THES) without intractable diarrhoea
We report an 8 year old girl who was diagnosed with THES by the Undiagnosed Disease Program-WA with compound heterozygous pathogenic variants in SKIV2L
Published research Computational BiologyMarch 2019A Diagnosis for All Rare Genetic Diseases: The Horizon and the Next Frontiers
There is a critical need for the field to develop and implement strategies to understand the mechanisms underlying all rare diseases and translate these to clinical care
Published research Computational BiologyJanuary 2019C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution.
We introduce C1 CAGE, a method for the detection of transcript 5'-ends with an original sample multiplexing strategy in the C1TM microfluidic system
Published research Computational BiologyDecember 2018Integration of genetics and miRNA-target gene network identified disease biology implicated in tissue specificity
Our result highlighted that miRNA-target gene network contributes to human disease genetics in a cell type-specific manner
Published research Computational BiologyNovember 2018Elucidating the interaction of CF airway epithelial cells and rhinovirus: Using the host-pathogen relationship to identify future therapeutic strategies
A better understanding of the innate immune responses by CF airway epithelial cells is needed to identify why viral infections are more severe in CF
Cystic Fibrosis Published research Computational Biology Airway Epithelial Research P4 Respiratory Health for KidsAugust 2018Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli
We obtain a set of 57 candidate immediate early genes possessing promoters that consistently drive a rapid but transient increase in expression over time
Published research Computational BiologyJuly 2018Arylsulphatase A Pseudodeficiency (ARSA-PD), hypertension and chronic renal disease in Aboriginal Australians
Traits associated with CVD, CRD and T2D in Aboriginal Australians provide novel insight into function of Arylsulphatase A Pseudodeficiency variants
Published research Aboriginal Health Diabetes and Obesity Computational Biology Genetics and HealthJune 2018Discovery of Transcription Factors Novel to Mouse Cerebellar Granule Cell Development Through Laser-Capture Microdissection
This study provides an initial insight into the TFs of cerebellar granule cells that might be important for development
Published research Computational BiologyApril 2018Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
A comprehensive in depth gene expression/regulation profile in Mycobacterium tuberculosis-infected macrophages
Published research Computational BiologyMarch 2017Transcription start site profiling of 15 anatomical regions of the Macaca mulatta central nervous system
We believe this data represents a useful resource to understand the central nervous system in macaque.
Published research Genetics and HealthFebruary 2018A phenotype centric benchmark of variant prioritisation tools
We hypothesised that the performance of variant prioriisation tools may vary by disease phenotype.
Published research Computational BiologyOctober 2017Linking FANTOM5 CAGE peaks to annotations with CAGEscan
Here, we present the production and quality control of CAGEscan libraries from 56 FANTOM5 RNA sources
Published research Computational BiologyNovember 2017Data Descriptor: Monitoring transcription initiation activities in rat and dog
The promoter landscape of several non-human model organisms is far from complete
Published research Computational BiologyOctober 2017Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes
Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in hepatocytes
Published research Computational BiologyOctober 2017Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC
Epigenetically regulated genes have a great theranostic potential, especially in tumors with no apparent driver mutations.
Published research Computational BiologySeptember 2017An integrated expression atlas of miRNAs and their promoters in human and mouse
We provided a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA.
Published research Computational BiologySeptember 2017Systematic analysis of transcription start sites in avian development
CAGE in combination with single-molecule sequencing technology allows mapping of TSSs and genome-wide capture of promoter activities state cell populations.
Published research Computational BiologyAugust 2016FANTOM5 CAGE profiles of human and mouse samples
Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells.
Genetics and Health Professional StaffMarch 2017An atlas of human long non-coding RNAs with accurate 5′ ends
Combining these findings with conservation data, we identify 19,175 potentially functional lncRNAs in the human genome.
Published research Genetics and HealthMarch 2017Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.
We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria.
Published research InflammationJanuary 2017Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution
Our results suggest a complex but highly coordinated regulation of adipogenesis
Published research Computational BiologyJanuary 2017Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin
Identified romidepsin as a promising therapeutic for mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia
Children's Cancers Published research Academic Biostatistics Leukaemia Translational Research Computational BiologyDecember 2016On-the-fly selection of cell-specific enhancers, genes, miRNAs and proteins across the human body using SlideBase
SlideBase, a web tool which offers a new way of selecting genes, promoters, enhancers and microRNAs that are preferentially expressed/used in a specified set of cells/tissues
Published research Computational BiologySeptember 2016CAGEd-oPOSSUM: motif enrichment analysis from CAGE-derived TSSs
CAGEd-oPOSSUM can identify transcription factors that act as key regulators of genes involved in specific mammalian cell and tissue types
Published research Computational BiologyApril 2016Reference genotype and exome data from an Australian Aboriginal population for health-based research
This data set provides a useful reference point for genomic studies on Aboriginal Australians
Published research Aboriginal Health Computational Biology Genetics and HealthJanuary 2016The rare and undiagnosed diseases diagnostic service – application of massively parallel sequencing in a state-wide clinical service
The Rare and Undiagnosed Diseases Diagnostic Service refers to a genomic diagnostic platform operating within the Genetic Services of Western Australia
Published research Computational Biology Genetics and HealthJanuary 2016Functional annotation of the vlinc class of non-coding RNAs using systems biology approach
We show that vlincRNAs genes likely function in cis to activate nearby genes
Published research Computational BiologyJanuary 2016Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers
Genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential
Published researchJanuary 2016DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C
The role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability
Published researchJanuary 2016Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin
Present a valuable resource for drug discovery and have identified ROM as a promising therapeutic for MLL-rearranged iALL
Published research Leukaemia Translational Research Computational BiologyNovember 2015Mapping mammalian cell-type-specific transcriptional regulatory networks using KD-CAGE and ChIP-seq data in the TC-YIK cell line.
Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct...
Published research Computational BiologyNovember 2015DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium
VEGFR-3 signaling plays a central role in lymphatic biology, both in the development of the lymphatic network during embryogenesis as well as in...
Published research Computational BiologyNovember 2015Application of Gene Expression Trajectories Initiated from ErbB Receptor Activation Highlights the Dynamics of Divergent Promoter Usage
This study helps us understand how cancer cells are regulated by key genes and their corresponding networks to alter their fate in response to specific...
Published research Computational BiologyJuly 2015Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ERBB receptors in breast cancer cells
The analysis of CAGE (Cap Analysis of Gene Expression) time-courses has been applied to examine the dynamics of enhancer and promoter by sequentially...
Published research Computational BiologyApril 2015Transcriptional dynamics reveal critical roles for non-coding RNAs in the immediate-early response
The immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers.
Published research Computational BiologyApril 2015Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells
Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during...
Published research Computational BiologyFebruary 2015Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells
The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors...
Published research Computational BiologyJanuary 2015Telomerase reverse transcriptase regulates microRNAs.
This study reports that telomerase reverse transcriptase extensively affects the expression levels of mature microRNAs.
Published research Computational BiologyJanuary 2015TagDust2: A generic method to extract reads from sequencing data.
Arguably the most basic step in the analysis of next generation sequencing data (NGS) involves the extraction of mappable reads from the raw reads...
Published research Computational BiologyJanuary 2015Gateways to the FANTOM5 promoter level mammalian expression atlas
The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE.
Published research Computational BiologyDecember 2014CAGE-defined promoter regions of the genes implicated in Rett Syndrome
A comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome
Published research Rett Syndrome Computational Biology