Laurence Ettwiller
@ettwiller.bsky.social
Scientist working at New England Biolabs. Tweets and comments represent my personal opinion and do not necessarily reflect the opinions of New England Biolabs.
Fantastic work from Weiwei Yang in collaboration with Shuang yong Xu, Nan Dai and Ivan Correa
October 24, 2025 at 12:56 PM
Fantastic work from Weiwei Yang in collaboration with Shuang yong Xu, Nan Dai and Ivan Correa
We also discovered new protein families potentially involved in dZ biosynthesis: DNA polymerases with enhanced dZ incorporation efficiency and nucleoside 2-deoxyribosyltransferases (NDTs) confirmed biochemically to catalyze dZ production.
October 24, 2025 at 12:56 PM
We also discovered new protein families potentially involved in dZ biosynthesis: DNA polymerases with enhanced dZ incorporation efficiency and nucleoside 2-deoxyribosyltransferases (NDTs) confirmed biochemically to catalyze dZ production.
Top hits matched known dZ biosynthesis enzymes, validating our hypothesis-free approach. Residue-level analysis pinpointed both known and novel amino acids in PurZ & YfbR-like dATPases, shedding light on substrate specificity.
October 24, 2025 at 12:56 PM
Top hits matched known dZ biosynthesis enzymes, validating our hypothesis-free approach. Residue-level analysis pinpointed both known and novel amino acids in PurZ & YfbR-like dATPases, shedding light on substrate specificity.
Using metaGPA, we linked protein families to the dZ modification phenotype. This analysis revealed 116 protein families significantly associated with phages predicted to contain dZ in their DNA.
October 24, 2025 at 12:56 PM
Using metaGPA, we linked protein families to the dZ modification phenotype. This analysis revealed 116 protein families significantly associated with phages predicted to contain dZ in their DNA.
While representative dZ biosynthetic pathway have been studied in lab isolates, the diversity & distribution of dZ phages in natural environments is largely unknown. We therefore developed a restriction–based enrichment method to isolate dZ-containing phages directly from aquatic metagenomes.
October 24, 2025 at 12:56 PM
While representative dZ biosynthetic pathway have been studied in lab isolates, the diversity & distribution of dZ phages in natural environments is largely unknown. We therefore developed a restriction–based enrichment method to isolate dZ-containing phages directly from aquatic metagenomes.
A wonderful collaboration with Dr. Jackson Buss, Dr. Kyle Brumfield and Dr. Rita R. Colwell
October 13, 2025 at 10:50 PM
A wonderful collaboration with Dr. Jackson Buss, Dr. Kyle Brumfield and Dr. Rita R. Colwell
This study demonstrates that it is possible to elicit and track functional responses directly within a microbiome, and to discover new enzymes in a hypothesis-free, reference-independent manner
October 13, 2025 at 10:50 PM
This study demonstrates that it is possible to elicit and track functional responses directly within a microbiome, and to discover new enzymes in a hypothesis-free, reference-independent manner
By searching for protein domains that mirrored this behavior (rather than relying on homology), she found GH18 to be the most significantly associated family — the very domain found in known chitinases.
October 13, 2025 at 10:50 PM
By searching for protein domains that mirrored this behavior (rather than relying on homology), she found GH18 to be the most significantly associated family — the very domain found in known chitinases.
Chitinases were expected to increase during the bait phase and be rapidly downregulated after the switch — providing a measurable, dynamic phenotype within the native microbiome.
October 13, 2025 at 10:50 PM
Chitinases were expected to increase during the bait phase and be rapidly downregulated after the switch — providing a measurable, dynamic phenotype within the native microbiome.
To make this possible, Colleen developed a “Bait-and-Switch” strategy:
first, she triggered a community succession toward chitin degraders (the bait), and then shifted the nutrient source to simple sugars (the switch).
first, she triggered a community succession toward chitin degraders (the bait), and then shifted the nutrient source to simple sugars (the switch).
October 13, 2025 at 10:50 PM
To make this possible, Colleen developed a “Bait-and-Switch” strategy:
first, she triggered a community succession toward chitin degraders (the bait), and then shifted the nutrient source to simple sugars (the switch).
first, she triggered a community succession toward chitin degraders (the bait), and then shifted the nutrient source to simple sugars (the switch).
Read the full story & explore the data here:
www.biorxiv.org/content/10.1...
👏 This is an amazing work from Amanda DeLiberto at #NEB @nebiolabs.bsky.social
#NGS #genomics #molecularbiology #preprint #contamination #sequencing
www.biorxiv.org/content/10.1...
👏 This is an amazing work from Amanda DeLiberto at #NEB @nebiolabs.bsky.social
#NGS #genomics #molecularbiology #preprint #contamination #sequencing
August 3, 2025 at 6:07 PM
Read the full story & explore the data here:
www.biorxiv.org/content/10.1...
👏 This is an amazing work from Amanda DeLiberto at #NEB @nebiolabs.bsky.social
#NGS #genomics #molecularbiology #preprint #contamination #sequencing
www.biorxiv.org/content/10.1...
👏 This is an amazing work from Amanda DeLiberto at #NEB @nebiolabs.bsky.social
#NGS #genomics #molecularbiology #preprint #contamination #sequencing
This dual-function strategy is ideal for:
🔹 Clinical & diagnostic sequencing
🔹 Low-input or precious samples
🔹 Metagenomics
🔹 Any workflow where contamination is a problem
🔹 Clinical & diagnostic sequencing
🔹 Low-input or precious samples
🔹 Metagenomics
🔹 Any workflow where contamination is a problem
August 3, 2025 at 6:07 PM
This dual-function strategy is ideal for:
🔹 Clinical & diagnostic sequencing
🔹 Low-input or precious samples
🔹 Metagenomics
🔹 Any workflow where contamination is a problem
🔹 Clinical & diagnostic sequencing
🔹 Low-input or precious samples
🔹 Metagenomics
🔹 Any workflow where contamination is a problem
Implementation is simple:
➕ Add Fpg & 7-deaza-dGTP directly to your PCR mix
⏱️ Brief pre-amplification incubation
No added steps, no workflow disruption
➕ Add Fpg & 7-deaza-dGTP directly to your PCR mix
⏱️ Brief pre-amplification incubation
No added steps, no workflow disruption
August 3, 2025 at 6:07 PM
Implementation is simple:
➕ Add Fpg & 7-deaza-dGTP directly to your PCR mix
⏱️ Brief pre-amplification incubation
No added steps, no workflow disruption
➕ Add Fpg & 7-deaza-dGTP directly to your PCR mix
⏱️ Brief pre-amplification incubation
No added steps, no workflow disruption
Why is this different?
7-deaza-dGTP is accepted by high-fidelity polymerases (unlike dUTP)
Fpg cleaves 7-deaza-dG-containing contaminants
Bonus: 7-deaza-dGTP reduces GC bias and improves sequencing coverage!
7-deaza-dGTP is accepted by high-fidelity polymerases (unlike dUTP)
Fpg cleaves 7-deaza-dG-containing contaminants
Bonus: 7-deaza-dGTP reduces GC bias and improves sequencing coverage!
August 3, 2025 at 6:07 PM
Why is this different?
7-deaza-dGTP is accepted by high-fidelity polymerases (unlike dUTP)
Fpg cleaves 7-deaza-dG-containing contaminants
Bonus: 7-deaza-dGTP reduces GC bias and improves sequencing coverage!
7-deaza-dGTP is accepted by high-fidelity polymerases (unlike dUTP)
Fpg cleaves 7-deaza-dG-containing contaminants
Bonus: 7-deaza-dGTP reduces GC bias and improves sequencing coverage!
Our method changes that.
We introduce a new strategy using:
✅ 7-deaza-dGTP
✅ Fpg glycosylase
Together, they provide similar carryover contamination removal as dUTP/UDG and work seamlessly in standard NGS pipelines.
We introduce a new strategy using:
✅ 7-deaza-dGTP
✅ Fpg glycosylase
Together, they provide similar carryover contamination removal as dUTP/UDG and work seamlessly in standard NGS pipelines.
August 3, 2025 at 6:07 PM
Our method changes that.
We introduce a new strategy using:
✅ 7-deaza-dGTP
✅ Fpg glycosylase
Together, they provide similar carryover contamination removal as dUTP/UDG and work seamlessly in standard NGS pipelines.
We introduce a new strategy using:
✅ 7-deaza-dGTP
✅ Fpg glycosylase
Together, they provide similar carryover contamination removal as dUTP/UDG and work seamlessly in standard NGS pipelines.
Contamination between NGS runs can compromise sensitive applications—from clinical diagnostics to ancient DNA.
Until now, enzymatic solutions like dUTP/UDG had one major flaw: they're are not compatible with high-fidelity NGS workflows.
Until now, enzymatic solutions like dUTP/UDG had one major flaw: they're are not compatible with high-fidelity NGS workflows.
August 3, 2025 at 6:07 PM
Contamination between NGS runs can compromise sensitive applications—from clinical diagnostics to ancient DNA.
Until now, enzymatic solutions like dUTP/UDG had one major flaw: they're are not compatible with high-fidelity NGS workflows.
Until now, enzymatic solutions like dUTP/UDG had one major flaw: they're are not compatible with high-fidelity NGS workflows.
(Sorry for the late reply - I was hiking the Alpine section of the GR5 trail over the past six days)
July 27, 2025 at 1:31 PM
(Sorry for the late reply - I was hiking the Alpine section of the GR5 trail over the past six days)
Phages containing dU can be sequenced using polymerases that tolerate dU, such as Taq or Q5U. But thermostable polymerases are not strictly required, as only the first round of amplification needs to successfully copy the dU-containing templates to allow their propagation in downstream PCR cycles.
July 27, 2025 at 1:31 PM
Phages containing dU can be sequenced using polymerases that tolerate dU, such as Taq or Q5U. But thermostable polymerases are not strictly required, as only the first round of amplification needs to successfully copy the dU-containing templates to allow their propagation in downstream PCR cycles.
dU containing phages have been described (for ex : PMID: 34033748, PMID: 35934259) while Mikael Skurnik's lab isolated YerA41, a Yersinia ruckeri Bacteriophage that cannot be sequenced due to bulky modifications (PMID: 32517038).
July 27, 2025 at 1:31 PM
dU containing phages have been described (for ex : PMID: 34033748, PMID: 35934259) while Mikael Skurnik's lab isolated YerA41, a Yersinia ruckeri Bacteriophage that cannot be sequenced due to bulky modifications (PMID: 32517038).
And yes- standard high-throughput sequencing misses bulky DNA modifications and those recognized as damage, like deoxyuridine (dU), because most standard protocols use high-fidelity polymerases that typically contain a dU pocket and stall at dU.
July 27, 2025 at 1:31 PM
And yes- standard high-throughput sequencing misses bulky DNA modifications and those recognized as damage, like deoxyuridine (dU), because most standard protocols use high-fidelity polymerases that typically contain a dU pocket and stall at dU.