About

Frank Albert, PhD, is an Associate Professor in the Department of Genetics, Cell Biology and Development at the University of Minnesota Medical School. His lab utilizes genomics, genome engineering, and synthetic biology to study how natural genetic variation influences gene expression and complex traits.

Research topics

• Biology
• Genetics
• Computational biology
• Physics
• Cell biology
• Evolutionary biology

Selected publications

• High-resolution genotype-free mapping of genetic variation with CRI-SPA-Map

  Genome Research · 2026-03-23

  preprintSenior author

  Genetic variation within species shapes phenotypes, but identifying the specific genes and variants that cause phenotypic differences is costly and challenging. Here, we introduce CRI-SPA-Map, a genetic mapping strategy combining CRISPR-Cas9 genome engineering, selective ploidy ablation (SPA), and high-throughput phenotyping for precise genetic mapping with or without genotyping in the yeast Saccharomyces cerevisiae . In CRI-SPA-Map, a donor strain carrying SPA machinery is mated to a genetically different recipient strain harboring a genome-integrated selectable cassette. In the resulting diploid, CRISPR-Cas9 cuts the cassette for replacement with DNA from the homologous donor chromosome. Donor chromosomes are then removed using SPA to yield haploid recombinant strains. To establish CRI-SPA-Map, we mate a W303 SPA strain to 92 strains from the BY4742 yeast knockout collection that carry gene deletion cassettes on the left arm of Chromosome XIV and create 1451 recombinant isolates. Whole-genome sequencing verifies that deletion cassette replacement introduces short donor DNA tracts of variable length, resulting in a finely recombined mapping population. Using only the known locations of the gene deletions, which mark where donor DNA is introduced, we identify a 6.5 kb region shaping yeast growth. We further dissect this region and identify two causal variants in two genes, MKT1 and SAL1 . Engineering these variants alone and in combination reveals gene-by-environment interactions at both genes, as well as epistatic interactions between them that are dependent on the environment. CRI-SPA-Map is a cost-effective, meiosis-free strategy for creating high-resolution recombinant panels of yeast strains for identifying the genetic basis of phenotypic variation.

  PublisherDOI

• Assembly of the infant gut microbiome and resistome are linked to bacterial strains in mother's milk

  Zenodo (CERN European Organization for Nuclear Research) · 2026-02-02

  datasetOpen access

  Supplementary Tables for the publication: "Assembly of the infant gut microbiome and resistome are linked to bacterial strains in mother’s milk" - Ferretti and Allert et al. Nature Communications 2025 The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as sole nutrition for the infant, little is known about how variation in the milk microbiome shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiomes using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. Microbial taxonomic overlap between milk and the infant gut was driven by Bifidobacterium longum, and infant microbiomes dominated by B. longum showed greater temporal stability than those dominated by other species. We identified numerous instances of strain sharing between milk and the infant gut, involving both commensal (e.g. B. longum) and pathobiont species (e.g. K. pneumoniae). Shared strains also included typically oral species such as S. salivarius and V. parvula, suggesting possible transmission from the infant’s oral cavity to the mother’s milk. At one month, the infant gut microbiome was enriched in biosynthetic pathways, suggesting that early colonisers might be more metabolically independent than those present at six months. Lastly, we observed significant overlap in antimicrobial resistance gene carriage within mother-infant pairs. Together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome. More info at: https://github.com/blekhmanlab/milk_infant_microbiome

  PublisherDOI

• Integration of 168,000 samples reveals global patterns of the human gut microbiome

  Cell · 2025-01-22 · 95 citations

  articleOpen access
  PublisherOA PDFDOI

• Trans-eQTL hotspots shape complex traits by modulating cellular states

  Cell Genomics · 2025-05-01 · 8 citations

  articleOpen accessSenior author

  Regulatory genetic variation shapes gene expression, providing an important mechanism connecting DNA variation and complex traits. The causal relationships between gene expression and complex traits remain poorly understood. Here, we integrated transcriptomes and 46 genetically complex growth traits in a large cross between two strains of the yeast Saccharomyces cerevisiae. We discovered thousands of genetic correlations between gene expression and growth, suggesting potential functional connections. Local regulatory variation was a minor source of these genetic correlations. Instead, genetic correlations tended to arise from multiple independent trans-acting regulatory loci. Trans-acting hotspots that affect the expression of numerous genes accounted for particularly large fractions of genetic growth variation and of genetic correlations between gene expression and growth. Genes with genetic correlations were enriched for similar biological processes across traits but with heterogeneous direction of effect. Our results reveal how trans-acting regulatory hotspots shape complex traits by altering cellular states.

  PublisherOA PDFDOI

• Genotype-by-environment interactions shape ubiquitin-proteasome system activity

  Genetics · 2025-08-29

  articleOpen accessSenior author

  In genotype-by-environment interactions (GxE), the effect of a genetic variant on a trait depends on the environment. GxE influences numerous organismal traits. However, we have limited understanding of how GxE shapes molecular processes. Here, we characterized how GxE shapes protein degradation, an essential molecular process that affects cellular and organismal physiology. Using 2 isolates of the yeast Saccharomyces cerevisiae, we profiled GxE in the ubiquitin-proteasome system (UPS), the primary protein degradation system in eukaryotes. By measuring UPS degradation activity toward 6 substrates that engage multiple distinct UPS pathways across 8 diverse environments, we discovered extensive GxE in the genetics of the UPS. The effects of all environments, including environments previously reported to affect UPS activity, differed between isolates and UPS substrates. To identify genomic regions underlying GxE for UPS activity, we mapped genetic influences on all our environment-UPS substrate combinations. Hundreds of locus effects varied depending on the environment. Most of these corresponded to loci that were present in one environment but not another ("presence/absence" GxE), while a smaller number of loci had opposing effects in different environments ("sign change" GxE). The number, genomic location, and type of GxE (presence/absence or sign change) of loci exhibiting GxE varied across UPS substrates. Loci exhibiting GxE were clustered at genomic regions that contain core UPS genes and at regions containing variation that affects the expression of thousands of genes, suggesting indirect contributions to UPS activity. Our results reveal complex interactions between the environment and the genetics of protein degradation.

  PublisherOA PDFDOI

• High-resolution, genotype-free mapping of genetic variation with CRI-SPA-Map

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-18

  preprintOpen accessSenior authorCorresponding

  Abstract Genetic variation within species shapes phenotypes, but identifying the specific genes and variants that cause phenotypic differences is costly and challenging. Here, we introduce CRI-SPA-Map, a genetic mapping strategy combining CRISPR-Cas9 genome engineering, selective ploidy ablation (SPA), and high-throughput phenotyping for precise genetic mapping with or without genotyping in the yeast Saccharomyces cerevisiae . In CRI-SPA-Map, a donor strain carrying SPA machinery is mated to a genetically different recipient strain harboring a genome-integrated selectable cassette. In the resulting diploid, CRISPR-Cas9 cuts the cassette for replacement with DNA from the homologous donor chromosome. Donor chromosomes are then removed using SPA to yield haploid recombinant strains. To establish CRI-SPA-Map, we mated a W303 SPA strain to 92 strains from the BY4742 yeast knockout collection that carry gene deletion cassettes on the left arm of chromosome XIV and created 1,451 recombinant isolates. Whole-genome sequencing verified that deletion cassette replacement introduced short donor DNA tracts of variable length, resulting in a finely recombined mapping population. Using only the known location of the gene deletions, which marks where donor DNA is introduced, we identified a 6.5 kb-region shaping yeast growth. Further dissection of this region pinpointed two causal variants in two genes, MKT1 and SAL1 . Engineering these variants alone and in combination revealed gene-by-environment interactions at both genes, as well as epistatic interactions between them that were in turn dependent on the environment. CRI-SPA-Map is a cost-effective strategy for creating high-resolution recombinant panels of yeast strains for identifying the genetic basis of phenotypic variation.

  PublisherOA PDFDOI

• Human Microbiome Compendium dataset

  Zenodo (CERN European Organization for Nuclear Research) · 2024-01-05

  datasetOpen access

  The Human Microbiome Compendium is an ongoing project to build a large collection of human microbiome sequencing data processed with a uniform pipeline. Currently, the compendium contains 16S rRNA amplicon sequencing data for human gut microbiome samples retrieved from the Sequence Read Archive. Our website at microbiomap.org has more information about the project and links to related resources. This data is freely available under a CC-BY license; if you use it in your work, please cite our preprint, "Integration of 168,000 samples reveals global patterns of the human gut microbiome" (doi: 10.1101/2023.10.11.560955). If you are using this dataset in conjunction with your own results, it's important to note that starting in version 1.0.1, the nomenclature used in this taxonomic table diverges from the output generated by DADA2 and the SILVA database. See the v1.0.1 release notes directly below for details. Version history 1.0.1: The "asv_assignments" table was corrected to fix entries in which the taxonomic levels were incorrectly inferred from the reference database by DADA2 (e.g. genus "Brassicibacter" was listed as a family, genus "Gelria" was listed as an order). The problem is documented in issues attached to repositories for DADA2, DADA2 reference databases, and our MicroBioMap library. In short, problems were noted in v138 of the SILVA database in which taxonomic names were not recorded properly if they were missing levels (e.g. a taxon has been assigned a proposed genus, but not a family). This was addressed in v138.1, which we originally used for generating this dataset. However, several dozen entries remain incorrectly annotated in v138.1—our 1.0.1 release corrects these by filling in the nomenclature gaps with "(unclassified)" and moving the existing data to the correct level. 2881 ASV assignments were affected out of about 4.3 million. The new file "taxa_corrections.tsv" is a copy of the "bad-taxa.csv" list generated by Michael McLaren, with notes added to reflect what we changed. 1.0.0: Added README.md file to the repository, and added a link to the preprint and title/author metadata for the Zenodo entry 0.2.1: "sample_metadata.tsv" was missing (Note: This was accidentally tagged "0.2.0" in the version history.) 0.2.0: Replacing "country" column in sample_metadata.tsv with an "iso" column using the country code rather than name. 0.1.0: Prepping for public release

  PublisherDOI

• Genotype-by-environment interactions shape ubiquitin-proteasome system activity

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-21

  preprintOpen accessSenior authorCorresponding

  Abstract In genotype-by-environment interactions (GxE), the effect of a genetic variant on a trait depends on the environment. GxE influences numerous organismal traits across eukaryotic life. However, we have a limited understanding of how GxE shapes the molecular processes that give rise to organismal traits. Here, we characterized how GxE shapes protein degradation, an essential molecular process that influences numerous aspects of cellular and organismal physiology. Using the yeast Saccharomyces cerevisiae , we characterized GxE in the activity of the ubiquitin-proteasome system (UPS), the primary protein degradation system in eukaryotes. By mapping genetic influences on the degradation of six substrates that engage multiple distinct UPS pathways across eight diverse environments, we discovered extensive GxE in the genetics of UPS activity. Hundreds of locus effects on UPS activity varied depending on the substrate, the environment, or both. Most of these cases corresponded to loci that were present in one environment but not another (“presence / absence” GxE), while a smaller number of loci had opposing effects in different environments (“sign change” GxE). The number of loci exhibiting GxE, their genomic location, and the type of GxE (presence / absence or sign change) varied across UPS substrates. Loci exhibiting GxE were clustered at genomic regions that contain core UPS genes and especially at regions containing variation that affects the expression of thousands of genes, suggesting indirect contributions to UPS activity. Our results reveal highly complex interactions at the level of substrates and environments in the genetics of protein degradation.

  PublisherOA PDFDOI

• Assembly of the infant gut microbiome and resistome are linked to bacterial strains in mother’s milk

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-28 · 6 citations

  preprintOpen access

  Abstract The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as sole nutrition for the infant, little is known about how variation in the milk microbiome shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiome using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. Microbial taxonomic overlap between milk and the infant gut was driven by Bifidobacterium longum , and infant microbiomes dominated by B. longum showed greater temporal stability than those dominated by other species. We identified numerous instances of strain sharing between milk and the infant gut, involving both commensal (e.g. B. longum ) and pathobiont species (e.g. K. pneumoniae ). Shared strains also included typically oral species such as S. salivarius and V. parvula , suggesting possible transmission from the infant’s oral cavity to the mother’s milk. At one month, the infant gut microbiome was enriched in biosynthetic pathways, suggesting that early colonisers might be more metabolically independent than later ones. Lastly, we observed significant overlap in antimicrobial resistance gene carriage within mother-infant pairs. Together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome.

  PublisherOA PDFDOI

• Chondroitin sulfate proteoglycan 4 increases invasion of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma by modifying transforming growth factor-β signalling

  British Journal of Dermatology · 2024-07-17 · 6 citations

  articleOpen access

  BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin-blistering disorder that often progresses to metastatic cutaneous squamous cell carcinoma (cSCC) at chronic wound sites. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell-surface proteoglycan that is an oncoantigen in multiple malignancies, where it modulates oncogenic signalling, drives epithelial-to-mesenchymal transition (EMT) and enables cell motility. OBJECTIVES: To evaluate CSPG4 expression and function in RDEB cSCC. METHODS: RDEB cSCC cell lines were used to assess CSPG4-dependent changes in invasive potential, transforming growth factor (TGF)-β1-stimulated signal activation and clinically relevant cytopathology metrics in an in vitro full-thickness tumour model. CSPG4 expression in RDEB cSCC and non-RDEB cSCC tumours was analysed via immunohistochemistry and single-cell RNA sequencing (scRNA-Seq), respectively. RESULTS: Inhibiting CSPG4 expression reduced invasive potential in multiple RDEB cSCC cell lines and altered membrane-proximal TGF-β signal activation via changes in SMAD3 phosphorylation. CSPG4 expression was uniformly localized to basal layer keratinocytes in fibrotic RDEB skin and tumour cells at the tumour-stroma interface at the invasive front in RDEB cSCC tumours in vivo. Analysis of published scRNA-Seq data revealed that CSPG4 expression was correlated with an enhanced EMT transcriptomic signature in cells at the tumour-stroma interface of non-RDEB cSCC tumours. Cytopathological metrics, for example nucleus : cell area ratio, were influenced by CSPG4 expression in in vitro tumour models. CONCLUSIONS: We determined that CSPG4 expression in RDEB cSCC cell lines enhanced the invasive potential of tumours. Mechanistically, CSPG4 was found to enhance membrane-proximal TGF-β-stimulated signalling via SMAD3, which is a key mediator of EMT in RDEB cSCC. The implication of these studies is that CSPG4 may represent a therapeutic target that can be leveraged for the clinical management of patients with RDEB cSCC.

  PublisherOA PDFDOI

Recent grants

• Causes and consequences of regulatory genetic variation

  NIH · $4.5M · 2017–2027

Frequent coauthors

• Leonid Kruglyak

  Howard Hughes Medical Institute

  43 shared

• Svante Pääbo

  Finland University

  37 shared

• Leif Andersson

  Texas A&M University

  19 shared

• Joshua S. Bloom

  19 shared

• Lyudmila N. Trut

  Institute of Cytology and Genetics

  16 shared

• François Besnier

  Montreal Heart Institute

  16 shared

• Irina Z. Plyusnina

  Institute of Cytology and Genetics

  16 shared

• José Blanco

  16 shared

Education

• PhD, Biology

  University of Leipzig

  2010

• Diplom, Biology

  University of Würzburg

  2005

• Visiting Fulbright Scholar

  University of Maryland

  2003