Franz Lang

Lund University

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Alexander Mjöberg

Lund University

Elizabeth Bjarnason

Lund University

Fabrice Douglas Rouah

McGill University

Gertraud Burger

Université de Montréal

Catherine Hankins

Amsterdam Institute for Global Health and Development

François Coutlée

Centre Hospitalier de l’Université de Montréal

Virginie Calderon

Montreal Clinical Research Institute

Mathieu Blanchette

McGill University

Sergey V. Steinberg

Université de Montréal

Mohamed Hafez

University of Manitoba

Cooperative Institutions

Université de Montréal

McGill University

Centre Hospitalier de l’Université de Montréal

Département de Chimie Moléculaire

Centre Hospitalier Universitaire Sainte-Justine

Weatherford College

Canadian Institute for Advanced Research

Université du Québec à Montréal

Institut National de Santé Publique

Institut National de Santé Publique du Québec

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Comparative analysis of organelle genomes, a biologist's view of computational challenges (abstract only)

Franz Lang

With genomic data (generated by classical, functional, structural, proteo- and other `omic' approaches) accumulating at a stupendous rate, there is an ever increasing need for the development of new, more efficient and more sensitive computational methods. To highlight aspects of our computational needs, we will present results that emerged from the comparative genome analysis of mitochondria. Having originated from an alpha-proteobacterial endosymbiont, these eukaryotic organelles contain small and extremely variable genomes, and are thus perfect model systems for the much more complex eubacterial and archaeal genomes. We are currently in vestigating mitochondrial DNAs (mtDNAs) in a lineage of unicellular, primitive protistan eukaryotes, the jakobids, with the aim to understand the evolution of mitochondrial genomes, genes and their regulation. Because these organisms are difficult to grow, biochemical approaches aimed at understanding gene regulation are laborious, thus it is possible to capitalize considerably from predictions on genome and gene organization, and regulatory elements. Contrary to approaches in which molecular data (gene order, sequence similarities) are used to infer the phylogenetic relationships among a group of organism, we know their phylogeny and employ this information to identify and model more or less conserved genetic elements and structural RNA genes that are difficult to spot by conventional methods, in a phylogenetic-comparative approach.

Lineage (genetic)

Organelle

10.1145/369133.369201

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A Model of Software Prototyping based on a Systematic Map

Elizabeth Bjarnason Franz Lang Alexander Mjöberg

Background: Prototyping is an established practice for user interface design and for requirements engineering within agile software development, even so there is a lack of theory on prototyping. Aims: The main research objective is to provide a means to categorise prototyping instances, in order to enable comparison and reflection of prototyping practices. Method: We have performed a systematic mapping study of methodological aspects of prototyping consisting of thirty-three primary studies upon which we designed a model of prototyping that was validated through a focus group at a case company. Results: Our model consists of four aspects of prototyping, namely purpose, prototype scope, prototype use, and exploration strategy. This model supported the focus group participants in discussing prototyping practices by considering concrete prototyping instances in terms of the concepts provided by our model. Conclusions: The model can be used to categorise prototyping instances and can support practitioners in reflecting on their prototyping practices. Our study provides a starting point for further research on prototyping and into how the practice can be applied more cost-effectively to elicit, validate, and communicate requirements.

Rapid Prototyping

Software prototyping

Scope (computer science)

10.1145/3475716.3475772

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Citations (12)

An empirically based model of software prototyping: a mapping study and a multi-case study

Empirical Software Engineering (2023)

Elizabeth Bjarnason Franz Lang Alexander Mjöberg

Abstract Context Prototyping is an established practice within product and user interface design that is also used as a requirements engineering (RE) practice within agile development. Even so, there is a lack of theory on prototyping. Aims Our main research objective is to support practitioners in improving on their prototyping practices. Method We have designed a model that describes key aspects of the practice of prototyping. The model is based on a systematic mapping study consisting of thirty-three primary studies and on empirical data from twelve case companies. We validate and demonstrate the applicability of our model through a focus group at one company and through semi-structured interviews at eleven (other) startup companies. Results Our prototyping aspects model (PAM) consists of five aspects of prototyping, namely purpose, prototype scope, prototype media, prototype use, and exploration strategy. This model has enabled practitioners to discuss their prototyping practices in terms of the concepts provided by our model. Conclusions The model can be used to categorise prototyping instances and can thereby support practitioners in reflecting and improving on their prototyping practices.

Rapid Prototyping

Scope (computer science)

Software prototyping

Virtual Prototyping

10.1007/s10664-023-10331-w

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Molecular Analysis of Human Papillomavirus Type 52 Isolates Detected in the Genital Tract of Human Immunodeficiency Virus–Seropositive and –Seronegative Women

The Journal of Infectious Diseases (2003)

Joséphine Aho Catherine Hankins Cécile Tremblay Franz Lang Pierre Forest

Human papillomavirus (HPV) type 52 DNA was detected in cervicovaginal lavage samples from 91 (12.4%) of 732 human immunodeficiency virus (HIV)–seropositive women and 23 (7.1%) of 323 HIV-seronegative women (P=.0004). HIV infection was an independent predictor for HPV-52 infection when controlling for age and sexual activity (odds ratio, 2.21; 95% confidence interval, 1.30–3.75: P=.003). We describe the genomic polymorphism of 114 HPV-52 isolates. Long control region (LCR) mutations defined 27 HPV-52 variants. Nearly 32% of HPV-52 isolates carried deletions in the LCR. E6 and E7 mutations defined 17 and 9 variants, respectively. Five nonsynonymous E6 mutations were clustered from amino acids 92 to 94, near the putative p53 binding area. White women were more frequently infected by the prototype strain than were women of African descent (P=.0001). The genetic diversity of HPV-52 should facilitate the investigation of the role of genomic variations in cervical disease

Nonsynonymous substitution

Sex organ

10.1086/379198

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CoreTracker: accurate codon reassignment prediction, applied to mitochondrial genomes

Bioinformatics (2017)

Emmanuel Noutahi Virginie Calderon Mathieu Blanchette Franz Lang Nadia El-Mabrouk

Codon reassignments have been reported across all domains of life. With the increasing number of sequenced genomes, the development of systematic approaches for genetic code detection is essential for accurate downstream analyses. Three automated prediction tools exist so far: FACIL, GenDecoder and Bagheera; the last two respectively restricted to metazoan mitochondrial genomes and CUG reassignments in yeast nuclear genomes. These tools can only analyze a single genome at a time and are often not followed by a validation procedure, resulting in a high rate of false positives.We present CoreTracker, a new algorithm for the inference of sense-to-sense codon reassignments. CoreTracker identifies potential codon reassignments in a set of related genomes, then uses statistical evaluations and a random forest classifier to predict those that are the most likely to be correct. Predicted reassignments are then validated through a phylogeny-aware step that evaluates the impact of the new genetic code on the protein alignment. Handling simultaneously a set of genomes in a phylogenetic framework, allows tracing back the evolution of each reassignment, which provides information on its underlying mechanism. Applied to metazoan and yeast genomes, CoreTracker significantly outperforms existing methods on both precision and sensitivity.CoreTracker is written in Python and available at https://github.com/UdeM-LBIT/CoreTracker.mabrouk@iro.umontreal.ca.Supplementary data are available at Bioinformatics online.

Python

10.1093/bioinformatics/btx421

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Citations (12)

Prototyping as a Requirements Engineering Technique

Franz Lang Alexander Mjöberg

Source

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Ancient origin of the integrin-mediated adhesion and signaling machinery

Proceedings of the National Academy of Sciences (2010)

Arnau Sebé-Pedrós Andrew J. Roger Franz Lang Nicole King Iñaki Ruiz‐Trillo

The evolution of animals (metazoans) from their unicellular ancestors required the emergence of novel mechanisms for cell adhesion and cell–cell communication. One of the most important cell adhesion mechanisms for metazoan development is integrin-mediated adhesion and signaling. The integrin adhesion complex mediates critical interactions between cells and the extracellular matrix, modulating several aspects of cell physiology. To date this machinery has been considered strictly metazoan specific. Here we report the results of a comparative genomic analysis of the integrin adhesion machinery, using genomic data from several unicellular relatives of Metazoa and Fungi. Unexpectedly, we found that core components of the integrin adhesion complex are encoded in the genome of the apusozoan protist Amastigomonas sp., and therefore their origins predate the divergence of Opisthokonta, the clade that includes metazoans and fungi. Furthermore, our analyses suggest that key components of this apparatus have been lost independently in fungi and choanoflagellates. Our data highlight the fact that many of the key genes that had formerly been cited as crucial for metazoan origins have a much earlier origin. This underscores the importance of gene cooption in the unicellular-to-multicellular transition that led to the emergence of the Metazoa.

Multicellular organism

10.1073/pnas.1002257107

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Citations (236)

A second eukaryotic group with mitochondrion-encoded tmRNA

RNA Biology (2013)

Mohamed Hafez Gertraud Burger Sergey V. Steinberg Franz Lang

In bacteria, stalled ribosomes are rescued by transfer-mRNA (tmRNA) that catalyzes two steps. First, a non-encoded alanine is added to the incomplete polypeptide chain by the tRNAAla-like portion of tmRNA, and second, the ribosome switches to the mRNA-like domain of tmRNA, thus resuming protein synthesis. Mitochondrial DNA (mtDNA)-encoded mt-tmRNA is so far only known from jakobid protists, but we posit that the corresponding ssrA gene may also reside in other mtDNAs. Here we present a highly sensitive covariance model built from jakobid ssrA genes that identifies previously unrecognized ssrA homologs in mtDNAs of oomycetes. These genes, located in previously unassigned genomic regions, are circular permuted as in α-Protobacteria, implying that pre-tmRNA is processed and the two pieces are held together by non-covalent interactions. RNA-Seq data from Phytophthora sojae confirm predicted processing sites as well as post-transcriptional addition of 3′ CCA, a prerequisite for tmRNAs to be charged with alanine by alanyl-tRNA synthetase. Structure modeling of oomycete tmRNAs infers that the mRNA-like domain is lacking as in jakobids. Features of mitochondrial tmRNAs include the G-U pair at position three of the acceptor stem, a hallmark of bacterial tmRNAs, and a T-loop sequence that differs from that of standard tRNAs and most bacterial tmRNAs, forming alternative, virtually isosteric tertiary interactions with the D-loop. The anticodon stem has two additional G-A base pairs formed between the D-loop and the variable region, shortening the length of the variable region to a single nucleotide.

10.4161/rna.25376

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Citations (18)