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Cancer Policy Related News from Washington DC and New NCI Appointments

Reportor: Stephen J. Williams, PhD.

Biden to announce appointees to Cancer Panel, part of initiative to cut death rate

The president first launched the initiative in 2016 as vice president.

By Mary Kekatos

July 13, 2022, 3:00 PM

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America This Morning

America This Morning

President Joe Biden will announce Wednesday his appointees to the President’s Cancer Panel, ABC News can exclusively reveal.

The Cancer Panel is part of Biden’s Cancer Moonshot Initiative, which was relaunched in February, with a goal of slashing the national cancer death rate by 50% over the next 25 years.MORE: Biden relaunches cancer ‘moonshot’ initiative to help cut death rate

Biden will appoint Dr. Elizabeth Jaffee, Dr. Mitchel Berger and Dr. Carol Brown to the panel, which will advise him and the White House on how to use resources of the federal government to advance cancer research and reduce the burden of cancer in the United States.

Jaffee, who will serve as chair of the panel, is an expert in cancer immunology and pancreatic cancer, according to the White House. She is currently the deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and previously led the American Association for Cancer Research.

PHOTO: In this Sept. 8, 2016, file photo, Dr. Elizabeth M. Jaffee of the Pancreatic Dream Team attends Stand Up To Cancer (SU2C), a program of the Entertainment Industry Foundation (EIF), in Hollywood, Calif.
In this Sept. 8, 2016, file photo, Dr. Elizabeth M. Jaffee of the Pancreatic Dream Team attends Stand Up To Cancer (SU2C), a program of the Entertainment Industry Foundation (EIF), in Hollywood, Calif.ABC Handout via Getty Images, FILE

Berger, a neurological surgeon, directs the University of California, San Francisco Brain Tumor Center and previously spent 23 years at the school as a professor of neurological surgery.

Brown, a gynecologic oncologist, is the senior vice president and chief health equity officer at Memorial Sloan Kettering Cancer Center in New York City. According to the White House, much of her career has been focused on eliminating cancer care disparities due to racial, ethnic, cultural or socioeconomic factors.

Additionally, First Lady Jill Biden, members of the Cabinet and other administration officials are holding a meeting Wednesday of the Cancer Cabinet, made up of officials across several governmental departments and agencies, the White House said.

The Cabinet will introduce new members and discuss priorities in the battle against cancer including closing the screening gap, addressing potential environmental exposures, reducing the number of preventable cancer and expanding access to cancer research.MORE: Long Island school district found to have higher rates of cancer cases: Study

It is the second meeting of the cabinet since Biden relaunched the initiative in February, which he originally began in 2016 when he was vice president.

Both Jaffee and Berger were members of the Blue Ribbon Panel for the Cancer Moonshot Initiative led by Biden.

The initiative has personal meaning for Biden, whose son, Beau, died of glioblastoma — one of the most aggressive forms of brain cancer — in 2015.

“I committed to this fight when I was vice president,” Biden said at the time, during an event at the White House announcing the relaunch. “It’s one of the reasons why, quite frankly, I ran for president. Let there be no doubt, now that I am president, this is a presidential, White House priority. Period.”

The initiative has several priority actions including diagnosing cancer sooner; preventing cancer; addressing inequities; and supporting patients, caregivers and survivors.

PHOTO: In this June 14, 2016, file photo, Dr. Carol Brown, physician at Memorial Sloan Kettering Cancer Center, gives a presentation, at The White House Summit on The United State of Women, in Washington, D.C.
In this June 14, 2016, file photo, Dr. Carol Brown, physician at Memorial Sloan Kettering Cancer Center, gives a presentation, at The White House Summit on The United State of Women, in Washington, D.C.NurPhoto via Getty Images, FILE

The White House has also issued a call to action to get cancer screenings back to pre-pandemic levels.

More than 9.5 million cancer screenings that would have taken place in 2020 were missed due to the COVID-19 pandemic, according to the National Institutes of Health.MORE: Louisiana’s ‘Cancer Alley’ residents in clean air fight

“We have to get cancer screenings back on track and make sure they’re accessible to all Americans,” Biden said at the time.

Since the first meeting of the Cancer Cabinet, the Centers for Disease Control and Prevention has issued more than $200 million in grants to cancer prevention programs, the Centers for Medicaid & Medicare Services implemented a new model to reduce the cost of cancer care, and the U.S. Patent and Trademark Office said it will fast-track applications for cancer immunotherapies.

ABC News’ Sasha Pezenik contributed to this report.

Biden to tap prominent Harvard cancer surgeon to head National Cancer Institute

Monica Bertagnolli brings leadership experience in cancer clinical trials funded by the $7 billion research agency

headshot of Monica Bertagnolli
Monica BertagnolliASCO; GLENN DAVENPORT

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President Joe Biden is expected to pick cancer surgeon Monica Bertagnolli as the next director of the National Cancer Institute (NCI). Bertagnolli, a physician-scientist at Brigham and Women’s Hospital, the Dana-Farber Cancer Center, and Harvard Medical School, specializes in gastrointestinal cancers and is well known for her expertise in clinical trials. She will replace Ned Sharpless, who stepped down as NCI director in April after nearly 5 years.

The White House has not yet announced the selection, first reported by STAT, but several cancer research organizations closely watching for the nomination have issued statements supporting Bertagnolli’s expected selection. She is “a national leader” in clinical cancer research and “a great person to take the job,” Sharpless told ScienceInsider.

With a budget of $7 billion, NCI is the largest component of the National Institutes of Health (NIH) and the world’s largest funder of cancer research. Its director is the only NIH institute director selected by the president. Bertagnolli’s expected appointment, which does not require Senate confirmation, drew applause from the cancer research community

Margaret Foti, CEO of the American Association for Cancer Research, praised Bertagnolli’s “appreciation for … basic research” and “commitment to ensuring that such treatment innovations reach patients … across the United States.” Ellen Sigal, chair and founder of Friends of Cancer Research, says Bertagnolli “brings expertise the agency needs at a true inflection point for cancer research.”

Bertagnolli, 63, will be the first woman to lead NCI. Her lab research on tumor immunology and the role of a gene called APC in colorectal cancer led to a landmark trial she headed showing that an anti-inflammatory drug can help prevent this cancer. In 2007, she became the chief of surgery at the Dana-Farber Brigham Cancer Center.

She served as president of the American Society of Clinical Oncology in 2018 and currently chairs the Alliance for Clinical Trials in Oncology, which is funded by NCI’s National Clinical Trials Network. The network is a “complicated” program, and “Monica will have a lot of good ideas on how to make it work better,” Sharpless says.

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One of Bertagnolli’s first tasks will be to shape NCI’s role in Biden’s reignited Cancer Moonshot, which aims to slash the U.S. cancer death rate in half within 25 years. NCI’s new leader also needs to sort out how the agency will mesh with a new NIH component that will fund high-risk, goal-driven research, the Advanced Research Projects Agency for Health (ARPA-H).

Bertagnolli will also head NCI efforts already underway to boost grant funding rates, diversify the cancer research workplace, and reduce higher death rates for Black people with cancer.

The White House recently nominated applied physicist Arati Prabhakar to fill another high-level science position, director of the White House Office of Science and Technology Policy (OSTP). But still vacant is the NIH director slot, which Francis Collins, acting science adviser to the president, left in December 2021. And the administration hasn’t yet selected the inaugural director of ARPA-H.

Correction, 22 July, 9 a.m.: This story has been updated to reflect that Francis Collins is acting science adviser to the president, not acting director of the White House Office of Science and Technology Policy.

Accelerating PROTAC drug discovery: Establishing a relationship between ubiquitination and target protein degradation

Curator: Stephen J. Williams, Ph.D.

PROTACs have been explored in multiple disease fields with focus on only few ligases like cereblon (CRBN), Von Hippel-Lindau (VHL), IAP and MDM2. Cancer targets like androgen receptor, estrogen receptor, BTK, BCL2, CDK8 and c-MET [[6], [7], [8], [9], [10], [11]] have been successfully targeted using PROTACs. A variety of BET family (BRD2, BRD3, and BRD4)- PROTACs were designed using multiple ligases; MDM2-based BRD4 PROTAC [12], CRBN based dBET1 [13] and BETd-24-6 [14] for triple-negative breast cancer, enhanced membrane permeable dBET6 [15], and dBET57 PROTAC [16]. PROTACs for Hepatitis c virus (HCV) protease, IRAK4 and Tau [[17], [18], [19]] have been explored for viral, immune and neurodegenerative diseases, respectively. Currently, the PROTAC field expansion to vast undruggable proteome is hindered due to narrow focus on select E3 ligases. Lack of reliable tools to rapidly evaluate PROTACs based on new ligases is hindering the progress. Screening platforms designed must be physiologically relevant and represent true PROTAC cellular function, i.e., PROTAC-mediated target ubiquitination and degradation.

In the current study, we employ TUBEs as affinity capture reagents to monitor PROTAC-induced poly-ubiquitination and degradation as a measure of potency. We established and validated proof-of-concept cell-based assays in a 96-well format using PROTACS for three therapeutic targets BET family proteins, kinases, and KRAS. To our knowledge, the proposed PROTAC assays are first of its kind that can simultaneously 1) detect ubiquitination of endogenous, native protein targets, 2) evaluate the potency of PROTACs, and 3) establish a link between the UPS and protein degradation. Using these TUBE assays, we established rank order potencies between four BET family PROTACs dBET1, dBET6, BETd246 and dBET57 based on peak ubiquitination signals (“UbMax”) of the target protein. TUBE assay was successful in demonstrating promiscuous kinase PROTACs efficiency to degrade Aurora Kinase A at sub-nanomolar concentrations within 1 h. A comparative study to identify changes in the ubiquitination and degradation profile of KRAS G12C PROTACs recruiting two E3 ligases (CRBN and VHL). All of the ubiquitination and degradation profiles obtained from TUBE based assays correlate well with traditional low throughput immunoblotting. Significant correlation between DC50 obtained from protein degradation in western blotting and UbMax values demonstrates our proposed assays can aid in high-throughput screening and drastically eliminate artifacts to overcome bottlenecks in PROTAC drug discovery.

To successfully set up HTS screening with novel PROTACs without pre-existing knowledge, we recommend the following steps. 1. Identify a model PROTAC that can potentially demonstrate activity based on knowledge in PROTAC design or in vitro binding studies. 2. Perform a time course study with 2–3 doses of the model PROTAC based on affinities of the ligands selected. 3. Monitor ubiquitination and degradation profiles using plate-based assay and identify time point that demonstrates UbMax. 4. Perform a dose response at selected time point with a library of PROTACs to establish rank order potency.

INTRODUCTION

Ubiquitination is a major regulatory mechanism to maintain cellular protein homeostasis by marking proteins for proteasomal-mediated degradation [1]. Given ubiquitin’s role in a variety of pathologies, the idea of targeting the Ubiquitin Proteasome System (UPS) is at the forefront of drug discovery [2]. “Event-driven” protein degradation using the cell’s own UPS is a promising technology for addressing the “undruggable” proteome [3]. Targeted protein degradation (TPD) has emerged as a new paradigm and promising therapeutic option to selectively attack previously intractable drug targets using PROteolytic TArgeting Chimeras (PROTACs) [4]. PROTACs are heterobifunctional molecules with a distinct ligand that targets a specific E3 ligase which is tethered to another ligand specific for the target protein using an optimized chemical linker. A functional PROTAC induces a ternary E3-PROTAC-target complex, resulting in poly-ubiquitination and subsequent controlled protein degradation [5]. Ability to function at sub-stoichiometric levels for efficient degradation, a significant advantage over traditional small molecules.

PROTACs have been explored in multiple disease fields with focus on only few ligases like cereblon (CRBN), Von Hippel-Lindau (VHL), IAP and MDM2. Cancer targets like androgen receptorestrogen receptor, BTK, BCL2, CDK8 and c-MET [[6][7][8][9][10][11]] have been successfully targeted using PROTACs. A variety of BET family (BRD2, BRD3, and BRD4)- PROTACs were designed using multiple ligases; MDM2-based BRD4 PROTAC [12], CRBN based dBET1 [13] and BETd-24-6 [14] for triple-negative breast cancer, enhanced membrane permeable dBET6 [15], and dBET57 PROTAC [16]. PROTACs for Hepatitis c virus (HCV) proteaseIRAK4 and Tau [[17][18][19]] have been explored for viral, immune and neurodegenerative diseases, respectively. Currently, the PROTAC field expansion to vast undruggable proteome is hindered due to narrow focus on select E3 ligases. Lack of reliable tools to rapidly evaluate PROTACs based on new ligases is hindering the progress. Screening platforms designed must be physiologically relevant and represent true PROTAC cellular function, i.e., PROTAC-mediated target ubiquitination and degradation.

Cellular PROTAC screening is traditionally performed using cell lines harboring reporter genes and/or Western blotting. While Western blotting is easy to perform, they are low throughput, semi-quantitative and lack sensitivity. While reporter gene assays address some of the issues, they are challenged by reporter tags having internal lysines leading to artifacts. Currently, no approaches are available that can identify true PROTAC effects such as target ubiquitination and proteasome-mediated degradation simultaneously. High affinity ubiquitin capture reagents like TUBEs [20] (tandem ubiquitin binding entities), are engineered ubiquitin binding domains (UBDs) that allow for detection of ultralow levels of polyubiquitinated proteins under native conditions with affinities as low as 1 nM. The versatility and selectivity of TUBEs makes them superior to antibodies, and they also offer chain-selectivity (-K48, -K63, or linear) [21]. High throughput assays that can report the efficacy of multiple PROTACs simultaneously by monitoring PROTAC mediated ubiquitination can help establish rank order potency and guide chemists in developing meaningful structure activity relationships (SAR) rapidly.

In the current study, we employ TUBEs as affinity capture reagents to monitor PROTAC-induced poly-ubiquitination and degradation as a measure of potency. We established and validated proof-of-concept cell-based assays in a 96-well format using PROTACS for three therapeutic targets BET family proteins, kinases, and KRAS. To our knowledge, the proposed PROTAC assays are first of its kind that can simultaneously 1) detect ubiquitination of endogenous, native protein targets, 2) evaluate the potency of PROTACs, and 3) establish a link between the UPS and protein degradation. Using these TUBE assays, we established rank order potencies between four BET family PROTACs dBET1, dBET6, BETd246 and dBET57 based on peak ubiquitination signals (“UbMax”) of the target protein. TUBE assay was successful in demonstrating promiscuous kinase PROTACs efficiency to degrade Aurora Kinase A at sub-nanomolar concentrations within 1 h. A comparative study to identify changes in the ubiquitination and degradation profile of KRAS G12C PROTACs recruiting two E3 ligases (CRBN and VHL). All of the ubiquitination and degradation profiles obtained from TUBE based assays correlate well with traditional low throughput immunoblotting. Significant correlation between DC50 obtained from protein degradation in western blotting and UbMax values demonstrates our proposed assays can aid in high-throughput screening and drastically eliminate artifacts to overcome bottlenecks in PROTAC drug discovery.

Fig. 1. Schematic representation of TUBE assay to monitor PROTAC mediated cellular ubiquitination of target proteins.
Fig. 2. TUBE based assay screening of PROTACs: Jurkat cell lysates were treated with BRD3-specific PROTACs A) dBET1, B) dBET6, C) BETd24-6, and D) dBET57. Polyubiquitination profiles and Ubmax of BRD3 for each PROTAC were represented as relative CL intensity. Relative CL intensities were calculated by dividing raw CL signals from a given PROTAC dose over DMSO treated samples. Error bars represent standard deviations, n = 3.
Fig. 3. PROTAC mediated degradation of bromodomain proteins analyzed by anti-BRD3 western blotting. Dose response of PROTACs dBET1, dBET6, Betd-24-6 and dBET57 at 45 min in Jurkat cells demonstrates degradation of BRD3, Acting as loading control.

 

 

 

 

 

 

 

 

 

Fig. 4. PROTAC mediated ubiquitination and degradation of AURKA in K562 cells. (A) Time course study to evaluate intracellular ubiquitination and degradation. (B) Western blot analysis of time course study: degradation kinetics (C) A dose response study to evaluate DC50 of the promiscuous kinase PROTAC in K562 cells. (D) Western blot analysis of dose response study to monitor degradation, GAPDH as loading control. Error bars represent standard deviation, n = 3.

SOURCE

https://www.sciencedirect.com/science/article/abs/pii/S0006291X22011792

Other articles of PROTACs in this Open Access Journal Include

The Vibrant Philly Biotech Scene: Proteovant Therapeutics Using Artificial Intelligence and Machine Learning to Develop PROTACs

The Map of human proteins drawn by artificial intelligence and PROTAC (proteolysis targeting chimeras) Technology for Drug Discovery

Live Conference Coverage AACR 2020 in Real Time: Monday June 22, 2020 Late Day Sessions

From High-Throughput Assay to Systems Biology: New Tools for Drug Discovery

 

2022 Albert Lasker Basic Medical Research Award for Integrins—Mediators of Cell-Matrix and Cell-Cell Adhesion

Reporter: Aviva Lev-Ari, PhD, RN

 

The three recipients of 2022 Albert Lasker Basic Medical Research Award For discoveries concerning the integrins—key mediators of cell-matrix and cell-cell adhesion in physiology and disease are:

  • Richard O. Hynes, Massachusetts Institute of Technology
  • Erkki Ruoslahti, Sanford Burnham Prebys
  • Timothy A. Springer, Boston Children’s Hospital/Harvard Medical School

2022 Basic Award video

https://www.youtube.com/watch?v=4k60P3Pnh30

Acceptance remarks

Watch 3 Videos
 
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Figure 1A: Pairs that bond
Two protein chains, α and ß, compose the heterodimeric integrins that span the cell membrane. The portion outside affixes to molecules in the extracellular matrix (ECM) or on other cells. Adherence through integrins triggers cytoskeleton assembly and vice versa. Such events can also influence the behavior of other proteins inside the cell. The image shows the matrix-cell type of integrin; a second type mediates cell-cell interactions.
Illustration: Cassio Lynm / © Amino Creative

Figure 1B: Families that stick together
Integrin α and ß subunit each belong to a family of proteins with a shared evolutionary ancestor. Individual members of the α and ß families combine in different ways to create 24 mammalian heterodimers that physically associate with a variety of molecules. In the ECM, these binding partners include collagen, laminin, and other RGD-containing proteins such as fibronectin and fibrinogen; on cells, these partners include proteins such as ICAM-1, which dwells on the surface of white blood cells and cells that line blood vessels. The first integrin identified, the platelet receptor, promotes blood clotting. LFA-1 helps immune cells fight infections in numerous ways.
Illustration: Cassio Lynm / © Amino Creative

Figure 2: Fleeting attachments, profound effects
By fostering adherence between cells and the ECM or other cells, integrins play a key role in a tremendous number of essential physiological interactions.
Illustration: Cassio Lynm / © Amino Creative

Figures Source: 

https://laskerfoundation.org/winners/integrins-mediators-of-cell-matrix-cell-adhesion/

 

Selected Publications – Discovery of Integrins

Cell-Matrix Interactions

Ruoslahti, E., Vaheri. A., Kuusela, P., and Linder, E. (1973). Fibroblast surface antigen: a new serum protein. Biochim. BiophysActa. 322, 352-358.

Hynes, R.O. (1973). Alteration of cell-surface proteins by viral transformation and by proteolysis. Proc. Natl. Acad. Sci. USA70, 3170-3174.

Pierschbacher, M.D., and Ruoslahti, E. (1984). Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature309, 30-33.

Pytela, R., Pierschbacher, M.D., and Ruoslahti, E. (1985). A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc. Natl. Acad. Sci. USA. 82, 5766-5770.

Pytela, R., Pierschbacher, M.D., Ginsberg, M.H., Plow, E.F., and Ruoslahti, E. (1986). Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp-specific adhesion receptors. Science231, 1559-1562.

Tamkun, J.W., DeSimone, D.W., Fonda, D., Patel, R.S., Buck, C., Horwitz, A.F., and Hynes, R.O. (1986). Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 46, 271-282.

Hynes, R.O. (1987). Integrins: a family of cell surface receptors. Cell48, 549-554.

Ruoslahti, E. (1996). RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697-715.

Hynes, R.O. (2002). Integrins: bidirectional allosteric signaling machines. Cell. 110, 673-687.

Cell-Cell Interactions

Kurzinger, K., Reynolds, T., Germain, R.N., Davignon, D., Martz, E., and Springer, T.A. (1981). A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure. J. Immunol. 127, 596-600.

Sanchez-Madrid, F., Nagy, J., Robbins, E., Simon, P., and Springer, T.A. (1983). A human leukocyte differentiation antigen family with distinct alpha subunits and a common beta subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J. Exp. Med. 158, 1785-1789.

Thompson, W.S., Miller, L.J., Schmalstieg, F.C., Anderson, D.C., and Springer, T.A. (1984). Inherited deficiency of the Mac-1, LFA-1, p150,95 glycoprotein family and its molecular basis. J. Exp. Med. 160, 1901-1905.

Kishimoto, T.K., Lee, A., Roberts, T.M., and Springer, T.A. (1987). Cloning of the beta subunit of the leukocyte adhesion proteins: homology to an extra-cellular matrix receptor defines a novel supergene family. Cell. 48, 681-690.

Makgoba. M.W., Sanders, M.E., Luce, G.E.G., Dustin, M.L., Springer, T.A., Clark, E.A., Mannoni, P., and Shaw, S. (1988). ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature331, 86-88.

Staunton, D.E., Dustin, M.L., and Springer, T.A. (1989). Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature. 339, 61-65.

Springer, T.A. (1990). Adhesion receptors of the immune system. Nature. 346, 425-434.

Lawrence, M.B., and Springer, T.A. (1991). Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 65, 859-873.

Luo, B.-H., Carman, C.V., and Springer, T.A. (2007) Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25, 619-647.

Li, J., Yan, J., and Springer, T.A. (2021). Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state. eLife. 10, 1-22. e73359. doi: 10.7554/eLife.73359.

SOURCE

Clarivate Analytics – a Powerhouse in IP assets and in Pharmaceuticals Informercials

Curator and Reporter: Aviva Lev-Ari, PhD, RN

We addressed in the past in several articles the emergence of Clarivate in its new life post Reuters years which ended by a SPAC IPO in 2019. This articles included:

  • Clarivate Analytics expanded IP data leadership by new acquisition of the leading provider of intellectual property case law and analytics Darts-ip

https://pharmaceuticalintelligence.com/2019/12/02/clarivate-analytics-expanded-ip-data-leadership-by-new-acquisition-of-the-leading-provider-of-intellectual-property-case-law-and-analytics-darts-ip/

  • Innovation and Patent Activity during COVID-19 from Clarivate – Survey Results Published

https://pharmaceuticalintelligence.com/2020/06/30/innovation-and-patent-activity-during-covid-19-from-clarivate-survey-result-published/

  • Chasing change: Innovation and patent activity during COVID-19

https://pharmaceuticalintelligence.com/2020/07/02/chasing-change-innovation-and-patent-activity-during-covid-19/

  • Potential Use of LPBI IP as Value Price Driver by Potential Acquirer: Assumptions per Asset Class

 https://pharmaceuticalintelligence.com/2019-vista/potential-use-of-lpbi-ip-as-value-price-driver-by-potential-acquirer-assumptions-per-asset-class/

  • AI Acquisitions by Big Tech Firms Are Happening at a Blistering Pace: 2019 Recent Data by CBI Insights

https://pharmaceuticalintelligence.com/2019/12/11/ai-acquisitions-by-big-tech-firms-are-happening-at-a-blistering-pace-2019-recent-data-by-cbiinsights/

  • WHAT ARE LPBI Group’s NEEDS in June 2019 – Aviva’s BOLD VISION on June 11, 2019

https://pharmaceuticalintelligence.com/2019-vista/what-are-lpbi-groups-needs-in-june-2019-avivas-bold-vision-on-june-11-2019/

  • Opportunities Map for LPBI Group’s three Intellectual Property Asset Classes of Digital Published Products in the Acquisition Arena

https://pharmaceuticalintelligence.com/2019-vista/opportunities-map-in-the-acquisition-arena/

  • Multiple Major Scientific Journals Will Fully Adopt Open Access Under Plan S

https://pharmaceuticalintelligence.com/2020/09/10/multiple-major-scientific-journals-will-fully-adopt-open-access-under-plan-s/

 

In this curation I wish to showcase Clarivate as a result of a successful SPAC as presented in Financial Times article

The Spac sponsor bonanza

 

https://www.ft.com/content/9b481c63-f9b4-4226-a639-238f9fae4dfc

Few have replicated Mr Klein’s success, which he achieved after using a Spac to take the data company Clarivate Analytics public in 2019

Please use the sharing tools found via the share button at the top or side of articles. Copying articles to share with others is a breach of FT.com T&Cs and Copyright Policy. Email licensing@ft.com to buy additional rights. Subscribers may share up to 10 or 20 articles per month using the gift article service. More information can be found here.
https://www.ft.com/content/9b481c63-f9b4-4226-a639-238f9fae4dfc

That moment in June in which Mr Klein and his partners cashed in more than $60m came after the stock had doubled to more than $20, in part thanks to a deal to buy the intellectual property management and technology company CPA Global. Onex and Barings, the two private equity firms that owned Clarivate before it went public via Mr Klein’s Spac, also sold stock at the same time.

Please use the sharing tools found via the share button at the top or side of articles. Copying articles to share with others is a breach of FT.com T&Cs and Copyright Policy. Email licensing@ft.com to buy additional rights. Subscribers may share up to 10 or 20 articles per month using the gift article service. More information can be found here.
https://www.ft.com/content/9b481c63-f9b4-4226-a639-238f9fae4dfc

Clarivate’s share price has since risen to $27.69, so the value of Mr Klein’s remaining stake has continued to swell and his investor group still holds shares worth $395m. The group also has separate warrants on top further augmenting their potential profit.

See Figure 

SPAC IPO, 11/2018, $10/share

–>>> Merger, 3/2019, $10/share

–>>>Clarivate PLC, 11/2020, $27/share

… asymmetry of Spac mathematics: the risk in Spacs falls most heavily on outside shareholders even as the return on investment for sponsors looks very promising indeed.

SOURCE

https://www.ft.com/content/9b481c63-f9b4-4226-a639-238f9fae4dfc

 

It worth exploring the synergies embedded in a potential acquisition of LPBI Groups Portfolio of IP Assets by Clarivate Analytics, a publishing company that has the infrastructure needed for promotion of LPBI Group’s content in Pharmaceutical Media, Medicine, Life Sciences and Health care and for Monetization of this content.

Portfolio of IP Assets

 

Near Term Investment Outlook for 2023: A Perspective from Advisors Potentially Affecting M&A Landscape

Curator: Stephen J. Williams, Ph.D.

The following is an adaptation from various reports and the forseen changes in forecast for different sectors as well as the general investment landscape for the near future (2022-2023). Of course projections may change given changes in undewrlying fundamentals.

Many financial advisors and professionals feel the U.S. is in a late-cycle for its economy, with a significant slowing of corporate earnings in the midst of higher than usual inflation {although inflation estimates are being halved from its current 8-10% for next year}.    Consensus investment strategies deemed favorable include US (not international) equities with high quality assest and away from cyclicals.  This represents the near end of a business cycle.  As growth returns and interest rates increase we may seen the entrance into a new business cycle, although this may not happen until later 2023.  In general, it is advised investors move out of cyclicals as the economy continues to slow and into large and mid cap US equities.

This change in landscape may be very favorable to the overall Health Care and Information Technology sectors.  In health care, Life Sciences Tools and Services as well as Medical Devices are expected to outperform.  In IT, IT Services, software and Networking are favored sectors while communication services like Publishing Services are considered to be Neutral to Unfavorable.

What does this mean for Life Sciences and Health Related small companies looking for an Exit or M&A strategies?

With higher interest rates, credit markets may continue to deteriote and companies may have to look toward Global Macro to find any funding through cash or credit markets.  Equity Hedge strategies may be neutral to unfavorable with Event Driven opportunities like distressed deals  unfavorable but most analysts do consider Merger Arbitrage as Event Driven strategy to be favorable.  A competitive and narrow merger and acquisition environment is expected to last through 2023.

A general consensus for a neutroal environment is seen for most Private Equity, although a more favorable environment for small and mid cap buyouts may exist.  Recent short term weakness in the IT sector has led to diminished exit valuations however this may be a good entry point for Growth Equity and Venture Capital.  Private Debt strategies look unfavorable due to potential US recessions and potential underwriting issues.  Therefore Favored Private Capital strategies include Private Equity for Small and Mid Cap Buyouts and Growth Equity and Venture Capital.

Sources:

https://www.wellsfargo.com/investment-institute/2022-midyear-outlook/

Deals to pick up in second half of 2022

All of the stars are aligned for there to be a flurry of deals activity across all areas of the sector despite the slow start to the year so far. Many large pharma players are flush with cash (particularly those that have COVID-19 treatments in their arsenal), biotech valuations have been normalizing after years of a boom market and the 2025 patent cliff is rapidly approaching, all making for a strong deal environment.

Given the broader labor changes, supply shortages and constantly changing supply chain strategies and operations, the focus on quality can be challenging to sustain. Yet the downside can have massive impacts on businesses, including the potential inability to manufacture products.

The long litany of macroeconomic and regulatory headwinds has CEOs looking for transactions that are easily integrated and will get cash off their balance sheet as inflationary pressures mount. 


Pharmaceutical & life sciences deals outlook

Increased scrutiny from the US Federal Trade Commission (FTC) around larger deals could mean that 2022 will be a year of bolt-on transactions in the $5 to $15 billion range as pharma companies take multiple shots on goal in order to make up for revenues lost to generic competition in the remainder of the decade. However, don’t rule out the potential for larger deals ⁠— consolidation is good for the health ecosystem and drives broader efficiency.

Expect to see big pharma picking up earlier stage companies to try and fill the pipeline gaps that are likely to start in 2024. While market conditions suggest bargain prices for biotech are possible, recent transactions indicate that pharma companies are still paying significantly above current trading prices (ranging from approximately 50 to 100% of current trading), but below the peak valuations of recent memory.

In the first few months of the year, semi-annualized deal value was down 58% from the same period last year, with companies investing just $61.7 billion so far. Only 137 deals were announced during that time, compared to 204 in the year-prior period.

Talk of drug pricing regulations continues in Washington as Congress bats around a pared down version of the Build Back Better plan. Expect some of that tension to ease in the fall if a new Congress takes on a different agenda.

Other areas of the sector like medical devices face similar headwinds from regulators, and continue to deal with a greater impact from semiconductor shortages. Even though semi-annualized deal value in the medical device space is down 85% from the same period the prior year, expect these companies to remain focused on M&A as the subsector searches for alternative forms of revenue ⁠— particularly from new consumer-centric technologies.

Macroeconomic headwinds and geopolitical tensions have created volatility in spending at CDMOs and CROs, limiting their willingness to deploy capital as the uncertainty persists. 

Source: https://www.pwc.com/us/en/industries/health-industries/library/pharma-life-sciences-deals-outlook.html

From the JP MorgAN Healthcare Conference

Deals Or No Deals, J.P. Morgan Sets The Tone For 2022

Collaborations, Not M&A, Dominate

  • 12 Jan 2022
·         OPINION
  • Mandy Jackson

Mandy Jackson@ScripMandy Mandy.Jackson@informausa.com

Executive Summary

No big buyouts were revealed during the annual J.P. Morgan Healthcare Conference for a third year in a row. Big pharma firms are in acquisition mode, but execs stress desire for easy integrations and scientific alliances. 

Biopharmaceutical industry players – and reporters – eagerly await merger and acquisition announcements going into the annual J.P. Morgan Healthcare Conference, hoping to scrutinize which big pharma is buying which other company for signs of what the deal-making environment will be like in the coming year. And in 2022, for the third year in a row, the meeting started with no big M&A deals.

Instead, Pfizer Inc.Novartis AGAmgen, Inc.Bristol Myers Squibb Company and others announced collaboration agreements. (Also see “Deal Watch: Bristol, Pfizer Lead Off J.P. Morgan Week With Two Deals Apiece” – Scrip, 11 Jan, 2022.)

They and their peers insisted during J.P. Morgan presentations and Q&A sessions as well as in interviews with Scrip that they do intend to invest in business development in 2022, but with a primary focus on smaller bolt-on acquisitions as well as licensing deals and collaboration agreements. Bolt-on deals have been the focus for the past few years. (Also see “The Pandemic Hurt, But EY Expects More Biopharma Deal-Making In 2021” – Scrip, 11 Jan, 2021.)

Amgen CEO Bradway On Deals: Good (Smaller) Opportunities Are Vast

By Mandy Jackson11 Jan 2022

Amgen is enthusiastic about deals of all sizes, including a new Arrakis collaboration, and is interested in large transactions like its Otezla buy – but Bradway said right-priced opportunities are fewer and farther between. 

Read the full article here 

While investors and others are clamoring for potential buyers to execute large transactions, Amgen CEO Robert Bradway made the astute – and as he pointed out, obvious – observation that there simply are more small, early-stage ventures to partner with than there are large, later-stage companies to acquire. Bradway also noted that while Amgen would like to buy another growing commercial-stage product like Otezla (apremilast), not only are few available but there are few assets at a price that still leaves value on the table for both companies’ investors.

Source: https://scrip.pharmaintelligence.informa.com/SC145698/Deals-Or-No-Deals-JP-Morgan-Sets-The-Tone-For-2022

Impact of New Regulatory Trends in M&A Deals

The following podcast from Pricewaterhouse Cooper Health Research Institute (called Next in Health) discusses some of the trends in healthcare M&A and is a great listen. However from 6:30 on the podcast discusses a new trend which is occuring in the healthcare company boardroom, which is this new focus on integrating companies that have proven ESG (or environmental, social, governance) functions within their organzations. As stated, doing an M&A deal with a company with strong ESG is looked favorably among regulators now.

Please click on the following link to hear a Google Podcast Next in Health episode

https://podcasts.google.com/feed/aHR0cHM6Ly9mZWVkcy5idXp6c3Byb3V0LmNvbS8xMjgyNjQ2LnJzcw?sa=X&ved=2ahUKEwil9sua2cf5AhUErXIEHaoTBQoQ9sEGegQIARAC

Other Related Articles on Life Sciences Investing Published in this Open Access Scientific Journal Include the Following:

Podcast Episodes by THE EUROPEAN VC
Tweets and Retweets by @pharma_BI and @AVIVA1950 for #NEVS at 2019 New England Venture Summit, December 4, 2019 at the Hilton in Boston, Dedham, MA, hosted by youngStartUp #NEVS
Leaders in Pharmaceutical Business Intelligence & youngStartup Ventures: Venture Summit Virtual Connect West, March 16th -18th 2021 featuring a dedicated Lifesciences / Healthcare Track  
Leader Profile: Family Offices – Impact Investing and Philanthropy – Health and the Life Sciences
37th Annual J.P. Morgan HEALTHCARE CONFERENCE: News at #JPM2019 for Jan. 10, 2019: Deals and Announcements
Real Time Coverage of BIO International Convention, June 3-6, 2019 Philadelphia Convention Center; Philadelphia PA

and  other related articles https://pharmaceuticalintelligence.com/page/3/?s=Life+Science+Investing

SOP for production of WordClouds for articles in the NEW GENRE Audio English-Spanish: BioMed e-Series – 18 Volumes in Medicine

Author: Aviva Lev-Ari, PhD, RN

LPBI Group’s SOP for production of WordClouds for articles in the NEW GENRE Audio English-Spanish: BioMed e-Series – 18 Volumes in Medicine https://pharmaceuticalintelligence.com/audio-english-spanish-biomed-e-series/

include the following steps:

  1. To master WordItOut.com
  2. To apply it to all the articles in the following e-Series: Series A: 6 volumes, Series B: two volumes, Series C: two volumes, Series D: four volumes, Series E: four volumes

How to Start?

In PART B of every Volume you will find the electronic Table of Contents (eTOCs) of the e-Book

EXCEPTIONS:

In Series C: Cancer Volume One, eTOCs is in A.2

In Series B: Genomics Volume Two eTOCs is in A.2

STEPS in Production of WordClouds for each article in an e-Book

1.  You sign in to WordItOut.com

2.  You review all the steps to produce a WordCloud from an MS Word File

3.  You click on the URL of the 1st article in Volume 1

4.  You copy the article into an MS Word File

5.  You use this file on WordItOut.com website to produce a WordCloud for the 1st article

6.  You edit the output by removing meaning less words like connective term: the a, an, all, some, more

7.  You RUN again on a file that does not include the terms REMOVED

8.  You select a Scheme of colors for background and for fonts – optimize contrast for visibility and legibility

9.  YOU MAINTAIN 8, above for all the articles in ONE volume

10.              YOUR FINAL WordCloud for ONE article you upload to the Media Gallery on our Website. You write as Legend Based on Article Title: Quote here Title. Produced on date by your name

11.              You go to the 1st article you ADD Media, this WordCloud you had produced BELOW the NAME of the Author, Curator, Reporter. YOU UPDATE the article with your WordCloud. You View Page for QA

12.              You move to repeat all of the above for 2nd article in the same volume

13.              When you complete ONE volume you announce that Volume X has all the WordClouds in it

14.              You move to other Volumes in the series you are working on. If it is Series A, then you continue with Volumes Two, Three, Four, Five, Six

15.              YOU START WITH VOLUME ONE AND LET ME KNOW how many hours it took to create all the wordClouds, N=number of articles in Volume One

16.              We will decide regarding other Volumes in the same series

Cardiothoracic surgeons at UC San Francisco performed the first robotically assisted mitral valve prolapse surgery in San Francisco.

Reporter: Aviva Lev-Ari, PhD, RN

Mitral valve surgery is performed when the heart’s mitral valve needs to be repaired. Traditionally, mitral valve surgery required opening the chest and putting the patient on heart-lung bypass to keep blood circulating during surgery. Since 2016, UCSF surgeons have been performing minimally invasive mitral valve surgery without having to open the sternum and with smaller incisions. Robotically assisted mitral valve surgery adds yet another level of precision.

“Robotically assisted mitral valve surgery allows us to make even smaller incisions with greater precision,” said Tom C. Nguyen, M.D., robotic heart surgeon and chief of Cardiothoracic Surgery at UCSF. “By using the robotic arms, we have more degrees of articulation than with our natural wrists. The robot also magnifies the surgical field 10X in 3D. Ultimately, this translates into more precise surgery with faster recovery.”

During the robotically assisted surgery, the surgeon looks through a 3D camera to see the mitral valve as well as other structures inside the heart. The surgeon uses the robotic surgical system to guide the robotic arms and movements of the surgical instruments.

“Every valve looks different, and the extraordinary 3D vision that the robot camera provides, is just a real step up from all the technologies we have been using in the past,” said Tobias Deuse, M.D., cardiac and transplant surgeon and director of Minimally-invasive Cardiac Surgery. “The camera, together with the increased mobility of the instruments, allows for a very thorough evaluation of the valve and helps us make good and long-lasting repairs.”

Thanks to these innovations, mitral valve patients have fewer complications and can be discharged within three-to-four days. This patient’s symptoms included increased fatigue and palpitations. Since the surgery, he is at home and his recovery is going well.

In addition to mitral valve surgery, there are plans for additional robotically assisted cardiothoracic surgeries, including removal of intracardiac tumors and myxomas as well as for coronary revascularization.

SOURCE

https://www.universityofcalifornia.edu/news/ucsf-performs-first-robotic-cardiac-surgery-san-francisco?utm_source=fiat-lux&utm_medium=internal-email&utm_campaign=article-general&utm_content=text

Other robotic surgeries currently being performed at UCSF

encompass a wide range of specialties and procedures, including:

  • removing cancerous tissue from the lungs, uterus, ovaries, colon, rectum, esophagus, bladder, prostate, head and neck, liver and pancreas. Other robotic surgeries are used for
  • the treatment of uterine fibroids and endometriosis, female pelvic organ prolapse repairs,
  • hernia repairs and
  • bariatric surgery.

Other related articles on Mitral Valve Repair published in this Open Access Online Scientific Journal include the following:

TricValve Transcatheter Bicaval Valves System – Interventional cardiologists at Cleveland Clinic have successfully completed the first implantation in North America

Reporter: Aviva Lev-Ari, PhD, RN

The Patient for this historic procedure:

An 82-year-old man presenting with severe symptomatic tricuspid regurgitation (TR) and right heart failure (RHF).

Expert Opinion: The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

https://pharmaceuticalintelligence.com/2022/04/20/tricvalve-transcatheter-bicaval-valves-system-interventional-cardiologists-at-cleveland-clinic-have-successfully-completed-the-first-implantation-in-north-america/

and another 64 articles

https://pharmaceuticalintelligence.com/?s=Mitral+valve

Explanation on “Results of Medical Text Analysis with Natural Language Processing (NLP) presented in LPBI Group’s NEW GENRE Edition: NLP” on Genomics content, standalone volume in Series B and NLP on Cancer content as Part B New Genre Volume 1 in Series C

NEW GENRE Edition, Editor-in-Chief: Aviva Lev-Ari, PhD, RN

Series B: Frontiers in Genomics Research NEW GENRE Audio English-Spanish

https://pharmaceuticalintelligence.com/audio-english-spanish-biomed-e-series/new-genre-audio-english-spanish-series-b-frontiers-in-genomics-research/new-genre-volume-two-latest-in-genomics-methodologies-for-therapeutics-gene-editing-ngs-and-bioinformatics-simulations-and-the-genome-ontology-series-b-volume-2/

PART A: The eTOCs in Spanish in Audio format AND the eTOCs in Bi-lingual format: Spanish and English in Text format

PART C: The Editorials of the original e-Books in English in Audio format

However,

PART B: The graphical results of Machine Learning (ML), Deep Learning (DL) and Natural Language Processing (NLP) algorithms AND the Domain Knowledge Expert (DKE) interpretation of the results in Text format – PART B IS ISSUED AS A STANDALONE VOLUME, named

https://pharmaceuticalintelligence.com/audio-english-spanish-biomed-e-series/new-genre-audio-english-spanish-series-b-frontiers-in-genomics-research/genomics-volume-2-results-of-medical-text-analysis-with-natural-language-processing-nlp/

 See only Graphic results in

Genomics, Volume 3: NLP results – 38 or 39 Hypergraph Plots and 38 or 39 Tree diagram Plots by Madison Davis

https://pharmaceuticalintelligence.com/biomed-e-books/genomics-orientations-for-personalized-medicine/genomics-volume-2-nlp-results-38-or-39-hypergraph-plots-and-38-or-39-tree-diagram-plots-by-madison-davis/

Series C: e-Books on Cancer & Oncology NEW GENRE Audio English-Spanish

https://pharmaceuticalintelligence.com/audio-english-spanish-biomed-e-series/new-genre-audio-english-spanish-series-c-e-books-on-cancer-oncology/new-genre-volume-one-cancer-biology-and-genomics-for-disease-diagnosis-series-c-volume-1%ef%bf%bc/

PART A:

PART A.1: The eTOCs in Spanish in Audio format AND

PART A.2: The eTOCs in Bi-lingual format: Spanish and English in Text format

PART B:

The graphical results of Medical Text Analysis with Machine Learning (ML), Deep Learning (DL) and Natural Language Processing (NLP) algorithms AND the Domain Knowledge Expert (DKE) interpretation of the results in Text format

See only graphics in

https://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/cancer-volume-1-nlp-results-12-hypergraph-plots-and-12-tree-diagram-plots-by-madison-davis/

PART C:

The Editorials of the original e-Book in English in Audio format

Sperm damage and fertility problem due to COVID-19

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Many couples initially deferred attempts at pregnancy or delayed fertility care due to concerns about coronavirus disease 2019 (COVID-19). One significant fear during the COVID-19 pandemic was the possibility of sexual transmission. Many couples have since resumed fertility care while accepting the various uncertainties associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), including the evolving knowledge related to male reproductive health. Significant research has been conducted exploring viral shedding, tropism, sexual transmission, the impact of male reproductive hormones, and possible implications to semen quality. However, to date, limited definitive evidence exists regarding many of these aspects, creating a challenging landscape for both patients and physicians to obtain and provide the best clinical care.

According to a new study, which looked at sperm quality in patients who suffered symptomatic coronavirus (COVID-19) infections, showed that it could impact fertility for weeks after recovery from the virus. The data showed 60% COVID-19 infected men had reduction in sperm motility and 37% had drop in sperm count, but, 2 months after recovery from COVID-19 the value came down to 28% and 6% respectively. The researchers also of the view that COVID-19 could not be sexually transmitted through semen after a person had recovered from illness. Patients with mild and severe cases of COVID-19 showed similar rate of drop in sperm quality. But further work is required to establish whether or not COVID-19 could have a longer-term impact on fertility. The estimated recovery time is three months, but further follow-up studies are still required to confirm this and to determine if permanent damage occurred in a minority of men.

Some viruses like influenza are already known to damage sperm mainly by increasing body temperature. But in the case of COVID-19, the researchers found no link between the presence or severity of fever and sperm quality. Tests showed that higher concentrations of specific COVID-19 antibodies in patients’ blood serum were strongly correlated with reduced sperm function. So, it was believed the sperm quality reduction cause could be linked to the body’s immune response to the virus. While the study showed that there was no COVID-19 RNA present in the semen of patients who had got over the virus, the fact that antibodies were attacking sperm suggests the virus may cross the blood-testis barrier during the peak of an infection.

It was found in a previous report that SARS-CoV-2 can be present in the semen of patients with COVID-19, and SARS-CoV-2 may still be detected in the semen of recovering patients. Due to imperfect blood-testes/deferens/epididymis barriers, SARS-CoV-2 might be seeded to the male reproductive tract, especially in the presence of systemic local inflammation. Even if the virus cannot replicate in the male reproductive system, it may persist, possibly resulting from the privileged immunity of testes.

If it could be proved that SARS-CoV-2 can be transmitted sexually in future studies, sexual transmission might be a critical part of the prevention of transmission, especially considering the fact that SARS-CoV-2 was detected in the semen of recovering patients. Abstinence or condom use might be considered as preventive means for these patients. In addition, it is worth noting that there is a need for studies monitoring fetal development. Therefore, to avoid contact with the patient’s saliva and blood may not be enough, since the survival of SARS-CoV-2 in a recovering patient’s semen maintains the likelihood to infect others. But further studies are required with respect to the detailed information about virus shedding, survival time, and concentration in semen.

References:

https://www.euronews.com/next/2021/12/21/covid-can-damage-sperm-for-months-making-it-harder-to-conceive-a-baby-a-new-study-finds

https://www.fertstert.org/article/S0015-0282(20)32780-1/fulltext

https://www.fertstertreviews.org/article/S2666-5719(21)00004-9/fulltext

https://www.fertstertscience.org/article/S2666-335X(21)00064-1/fulltext

https://www.fertstert.org/article/S0015-0282(21)02156-7/fulltext

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765654/

https://www.fertstert.org/article/S0015-0282(21)01398-4/fulltext

https://www.euronews.com/next/2021/08/27/do-covid-vaccines-affect-pregnancy-fertility-or-periods-we-asked-the-world-health-organiza

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predispose women to a higher incidence of egg aneuploidy. However, the exact genetic causes of aneuploid egg production remain unclear, making it difficult to diagnose infertility based on individual genetic variants in mother’s genome. Although, age is a predictive factor for aneuploidy, it is not a highly accurate gauge because aneuploidy rates within individuals of the same age can vary dramatically.

Researchers described a technique combining genomic sequencing with machine-learning methods to predict the possibility a woman will undergo a miscarriage because of egg aneuploidy—a term describing a human egg with an abnormal number of chromosomes. The scientists were able to examine genetic samples of patients using a technique called “whole exome sequencing,” which allowed researchers to home in on the protein coding sections of the vast human genome. Then they created software using machine learning, an aspect of artificial intelligence in which programs can learn and make predictions without following specific instructions. To do so, the researchers developed algorithms and statistical models that analyzed and drew inferences from patterns in the genetic data.

As a result, the scientists were able to create a specific risk score based on a woman’s genome. The scientists also identified three genes—MCM5, FGGY and DDX60L—that when mutated and are highly associated with a risk of producing eggs with aneuploidy. So, the report demonstrated that sequencing data can be mined to predict patients’ aneuploidy risk thus improving clinical diagnosis. The candidate genes and pathways that were identified in the present study are promising targets for future aneuploidy studies. Identifying genetic variations with more predictive power will serve women and their treating clinicians with better information.

References:

https://medicalxpress-com.cdn.ampproject.org/c/s/medicalxpress.com/news/2022-06-miscarriage-failure-vitro-fertilization-genomic.amp

https://pubmed.ncbi.nlm.nih.gov/35347416/

https://pubmed.ncbi.nlm.nih.gov/31552087/

https://pubmed.ncbi.nlm.nih.gov/33193747/

https://pubmed.ncbi.nlm.nih.gov/33197264/

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