Biology subjects

Johansson, B.

Publications and source records attributed to Johansson, B..

5 recordsLinked to original sources

bioRxiv2025

The 3D genome of pediatric B-cell precursor acute lymphoblastic leukemia

Whereas the molecular pathogenesis of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) has been studied extensively, its 3D chromatin landscape - of vast importance for gene regulation - remains poorly explored. Here, we applied Micro-C, a high-resolution variant of Hi-C, to 35 primary pediatric BCP ALL cases, spanning all major genetic subtypes. We present a complete view of the chromatin interaction landscape in childhood ALL, with resolutions reaching up to 5 kb in individual samples and 1 kb in the aggregated dataset. Somatic genetic aberrations - including fusion genes, aneuploidy, and structural variants - were found to profoundly reshape the 3D genome organization, impacting chromatin compartmentalization (A/B), topologically associating domain (TAD) architecture, and regulatory element positioning. Notably, chromosomal gains were associated with weakened TAD boundaries and widespread gene dysregulation. In addition, our analysis identified over 25,000 chromatin loops anchored at regulatory elements--e.g., enhancer-promoter loops--regulating the expression of more than 10,000 protein-coding genes. Among these, we highlight regulatory loops that drive gene expression differences between BCP ALL subtypes in the absence of concurrent somatic genetic aberrations, including the known driver genes HOXA9, FLT3, TP53, CD44, IKZF1, ERG, and XBP1. Taken together, our study gives unprecedented insights into chromatin organization and gene regulation in the leukemogenesis of BCP ALL.

cancer biology↗

bioRxiv2025

dnaudit + Pydnaweb: A lightweight text-based planning and documentation workflow for genetic cloning with automatic verification

Life science research often depends on the construction and analysis of recombinant DNA molecules, where sequence accuracy is critical. However, the field continues to face a reproducibility crisis, partly due to the lack of comprehensive, systematic, and verifiable documentation of genetic constructions. Although most cloning procedures are deterministic and theoretically describable in a complete and unambiguous way, published methods are typically described in a form free narrative, making them laborious to reproduce and assess for completeness. Tools like the Python package Pydna support programmable and reproducible cloning strategies but require coding expertise, which can be a barrier for some users. To address this, we developed Pydnaweb and dnaudit, two open-source and complementary web tools that build on Pydna. Pydnaweb offers simulation of unit operations such as PCR and restriction digestion providing results in text format. These results can be collected and combined to form complex cloning strategies in a bottom-up approach. Dnaudit can verify such collections for internal consistency and that the cloning strategy meet a specific goal such as the expression of a protein sequence. The tools are design for a low barrier of entry, and they can be used separately. This workflow enables fully automated validation, providing a no-code, reproducible solution for documenting and sharing molecular cloning workflows. These tools ease compliance with FAIR principles and align with emerging standards for the transparent and reproducible sharing of scientific methods and data.

bioinformatics↗

bioRxiv2024

SEGUID v2: Extending SEGUID checksums for circular, linear, single- and double-stranded biological sequences

BackgroundSynthetic biology involves combining different DNA fragments, each containing functional biological parts, to address specific problems. Fundamental gene-function research often requires cloning and propagating DNA fragments, such as those from the iGEM Parts Registry or Addgene, typically distributed as circular plasmids. Addgenes repository alone offers around 150,000 plasmids. To ensure data integrity, cryptographic checksums can be calculated for the sequences. Each sequence has a unique checksum, making checksums useful for validation and quick lookups of associated annotations. For example, the SEGUID checksum uniquely identifies protein sequences with a 27-character string. ObjectivesThe original SEGUID, while effective for protein sequences and single-stranded DNA (ssDNA), is not suitable for circular DNA since there is no natural starting position nor for double-stranded DNA (dsDNA) since two separate sequences are present. Challenges include how to uniquely represent linear dsDNA, circular ssDNA, and circular dsDNA. To meet these needs, we propose SEGUID v2, which extends the original SEGUID to handle additional types of sequences. ConclusionsSEGUID v2 produces orientation and rotation in-variant checksums for single-stranded, double-stranded, possibly staggered, linear, and circular DNA and RNA sequences. Customizable alphabets allow for other types of sequences. In contrast to the original SEGUID, which uses Base64, SEGUID v2 uses Base64url to encode the SHA-1 hash. This ensures SEGUID v2 checksums can be used as-is in filenames, regardless of platform, and in URLs, with minimal friction. AvailabilitySEGUID v2 is readily available for major program-ming languages, distributed under the MIT license. JavaScript package seguid is available on npm, Python package seguid on PyPi, R package seguid on CRAN, and a Tcl script on GitHub. These tools, along with documentation, examples, and an online SEGUID Calculator, can be found at https://www.seguid.org.

bioinformatics↗

bioRxiv2021

Bleeding in patients and mice with Alagille syndrome: sex differences and risk factors

Spontaneous lethal bleeds are major cause of death in the pediatric liver disease Alagille syndrome (ALGS), yet risk factors and screening methods have not been established. We performed a systematic review and identified significantly more female than male patients with idiopathic intracranial hemorrhage (10:1). We investigated bleeding and vasculature in patients and a mouse model for ALGS (Jag1Ndr/Ndr mice) and asked whether phenotypes identified in mice could be detected in patients non-invasively. Jag1Ndr/Ndr mice bled spontaneously, exhibiting a thin skull and vascular defects including artery-vein crossings, tortuous vessels, capillary breakdown and CADASIL-like sparse vascular smooth muscle cell coverage which was aggravated by hypertension. Retinographs from patients confirmed tortuous blood vessels and artery-vein crossings in ALGS. In conclusion, Jag1Ndr/Ndr mice could be used to develop interventions for vascular defects in ALGS, and retinography could provide a non-invasive method for vascular analysis in these pediatric patients.

developmental biology↗

bioRxiv2020

Consolidated bioprocessing of corn cob-derived hemicellulose: engineered industrial Saccharomyces cerevisiae as efficient whole cell biocatalysts

Consolidated bioprocessing, which combines saccharolytic and fermentative abilities in a single microorganism, is receiving increased attention to decrease environmental and economic costs in lignocellulosic biorefineries. Nevertheless, the economic viability of lignocellulosic ethanol is also dependent of an efficient utilization of the hemicellulosic fraction, which is mainly composed of xylose and may comprise up to 40 % of the total biomass. This major bottleneck is mainly due to the necessity of chemical/enzymatic treatments to hydrolyze hemicellulose into fermentable sugars and to the fact that xylose is not readily consumed by Saccharomyces cerevisiae – the most used organism for large-scale ethanol production. In this work, industrial S. cerevisiae strains, presenting robust traits such as thermotolerance and improved resistance to inhibitors, were evaluated as hosts for the cell-surface display of hemicellulolytic enzymes and optimized xylose assimilation, aiming at the development of whole-cell biocatalysts for consolidated bioprocessing of corn cob-derived hemicellulose. These modifications allowed the direct production of ethanol from non-detoxified hemicellulosic liquor obtained by hydrothermal pretreatment of corn cob, reaching an ethanol titer of 11.1 g/L corresponding to a yield of 0.328 gram per gram of potential xylose and glucose, without the need for external hydrolytic catalysts. Also, consolidated bioprocessing of pretreated corn cob was found to be more efficient for hemicellulosic ethanol production than simultaneous saccharification and fermentation with addition of commercial hemicellulases. These results show the potential of industrial S. cerevisiae strains for the design of whole-cell biocatalysts and paves the way for the development of more efficient consolidated bioprocesses for lignocellulosic biomass valorization, further decreasing environmental and economic costs.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗